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Review

Bee Stressors from an Immunological Perspective and Strategies to Improve Bee Health

1
Pharmacognosy Group, Department of Pharmaceutical Biosciences, Uppsala University, Biomedical Centre, P.O. Box 591, SE 751 24 Uppsala, Sweden
2
International Research Center for Food Nutrition and Safety, Jiangsu University, Zhenjiang 212013, China
3
International Joint Research Laboratory of Intelligent Agriculture and Agri-Products Processing (Jiangsu University), Jiangsu Education Department, Nanjing 210024, China
4
Department of Chemistry, Faculty of Science, Menoufia University, Shebin El-Kom 32512, Egypt
5
Department of Bee Research, Plant Protection Research Institute, Agricultural Research Centre, Giza 12627, Egypt
6
Department of Chemistry, Quaid-I-Azam University, Islamabad 45320, Pakistan
7
Al nahal al jwal Foundation Saudi Arabia, P.O. Box 617, Al Jumum, Makkah 21926, Saudi Arabia
8
Chemistry Division, National Institute of Standards, 136, Giza 12211, Egypt
9
School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China
10
H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan
11
Department of Pharmaceutical Chemistry, Kulliyyah of Pharmacy, International Islamic Univetsity Malaysia, Kuantan 25200, Malaysia
12
Faculty of Pharmacy, Universitas Airlangga, Surabaya 60155, Indonesia
13
Biology Department, Faculty of Science, Taibah University, Al Madinah 887, Saudi Arabia
14
Zoology Department, Faculty of Science, Tanta University, Tanta 31527, Egypt
15
General Zoology, Institute for Biology, Martin Luther University Halle-Wittenberg, Hoher Weg 8, 06120 Halle, Germany
16
Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, SE 106 91 Stockholm, Sweden
17
Institute of Apicultural Research, Chinese Academy of Agricultural Sciences, Beijing 100093, China
*
Authors to whom correspondence should be addressed.
Vet. Sci. 2022, 9(5), 199; https://doi.org/10.3390/vetsci9050199
Submission received: 11 March 2022 / Revised: 11 April 2022 / Accepted: 14 April 2022 / Published: 21 April 2022
(This article belongs to the Special Issue Challenges and Advances in Bee Health and Diseases)

Abstract

:
Honeybees are the most prevalent insect pollinator species; they pollinate a wide range of crops. Colony collapse disorder (CCD), which is caused by a variety of biotic and abiotic factors, incurs high economic/ecological loss. Despite extensive research to identify and study the various ecological stressors such as microbial infections, exposure to pesticides, loss of habitat, and improper beekeeping practices that are claimed to cause these declines, the deep understanding of the observed losses of these important insects is still missing. Honeybees have an innate immune system, which includes physical barriers and cellular and humeral responses to defend against pathogens and parasites. Exposure to various stressors may affect this system and the health of individual bees and colonies. This review summarizes and discusses the composition of the honeybee immune system and the consequences of exposure to stressors, individually or in combinations, on honeybee immune competence. In addition, we discuss the relationship between bee nutrition and immunity. Nutrition and phytochemicals were highlighted as the factors with a high impact on honeybee immunity.

Graphical Abstract

1. Introduction

The European honeybees (Apis mellifera L.) is considered one of the most important agricultural pollinators worldwide. They play a key role in food productivity by pollinating various plants [1,2]. One-third of a person’s diet comes from insect-pollinated plants, and honeybees are responsible for the pollination of over 80% of flowering plants. Without honeybees pollination, crop yields would decrease by >90% [3]. Therefore, there is major international concern related to bee colony loss [4,5]. Overall, 52 of the 115 leading world food commodities rely on honeybees. Thus, in the honeybees loss scenario, fruit quality or quantity yields would be reduced for 16 commodities (by 90–40%), modestly reduced (10–40%) for 19 commodities, and somewhat reduced (by 10%) for 13 commodities [3]. Pollination fees for blooming cherries, plums, and almonds have increased. For example, almond pollination fees have increased by ~180%; this increase mainly occurred between 2004 and 2006. Previous study estimated that a 10% rise in the bees colony’s winter death rate results in 16% drop in overall almond pollination revenue [6].
Colony collapse disorder (CCD), which first emerged in the US in 2006, caused huge colony losses and posed challenges for crop pollination, which is the major service of the apicultural industry in North America [7]. The observed losses between 1961 and 2007 recorded in Europe and North America were 26.5% and 49.5%, respectively. Honeybee colonies have increased, primarily in Asia (426%), Africa (130%), South America (86%), and Oceania (39%) [8]. The following factors have been implicated in honeybee losses in different parts of the world: honeybee diseases, parasites, in-hive chemical substances, agrochemicals, genetically modified (GM) plants, modified land-use, changed and alteration in the cultural practices, beekeeping practices, as well as the climate change [9,10,11,12,13,14].
Although most scientists understand the multiple origins of bee colony losses, a full understanding of the mechanistic basis of this devastating occurrence is required. What is the common trend in colony losses that can be linked to diverse stress factors depending on the circumstances? How can bees respond to a comprehensive environmental challenge with a coordinated stress response against biotic and abiotic stress agents, which frequently have a synergistic effect and result in a considerably stronger negative impact of parasites and pathogens (often coexisting in complicated associations)?. These are the most pressing issues that must be addressed [15].

2. Honeybee Immunity

The widespread agreement on the multifactorial origins of colony collapse and its frequent correlation with high pathogen and parasite loads indicate that the immune system is the most targeted, and its activity can be altered by a variety of stressors [15]. Bees have an innate immune system, which includes physical barriers, cellular, and humoral responses to defend against pathogens and parasites. The physical barrier includes an exoskeleton cuticle and the peritrophic membranes lining the digestive tract to prevent the entry of pathogenic organisms into the body cavity [16]. The recognition of pathogen-associated molecular patterns by recognition receptors triggers the innate immune system [17]. As a result, hemocytes that represent the primary mediators of cellular immunity will be activated, including phagocytosis, nodule formation, encapsulation, as well as the initiation of phenol-oxidase that regulates coagulation or melanization, or the synthesis of antimicrobial peptides (AMP), such as abaecin, apidaecin, hymenoptaecin, and defensin [18]. The immune system of honeybees possesses orthologues for the major members of immune pathways comprising the following: Toll (transmembrane signal transduction pathway), immune deficiency (Imd), Jun-N-terminal kinase, and JAK/STAT (Janus kinase/signal transducers and activators of transcription). RNA interference (RNAi), known as RNA silencing, is an important antiviral defense mechanism in insects, including honeybees. The efficacy of RNAi-mediated treatment against honeybee viruses and the fact that honeybee viruses encode for putative virus-encoded suppressors of RNAi shows that RNAi is an important honeybee antiviral defense mechanism [10,19]. In addition, several studies implicate the involvement of innate immune pathways (Jak-STAT, Toll, and Imd) and non-sequence-specific dsRNA-mediated antiviral defense as part of the immune responses in honeybee [20].
Bees are creatures that exhibit social immunity to prevent parasite infection from spreading among colony members. Honeybee workers use hygienic practices to remove diseased brood [21]. Furthermore, social fever develops when bees cooperate to raise the temperature within the colony to resist the heat-sensitive fungal disease Ascosphaera apis, known as chalkbrood disease [22]. Grooming, which is the physical removal of parasitic mites from the bodies of adult bees by individual workers or their nest-mates, is one of the most important defense modes against the ectoparasitic mite Varroa destructor [23]. Other mechanisms of social immunity such as propolis collection is used for nest constriction. It helps in declining investment in the immune response of 7-day-old bees and enriches the health and productivity of the colony [24]. Previous study showed that a propolis envelope reduced the clinical symptoms of American foulbrood (AFB) two months after the challenge, compared with those of colonies without a propolis envelope. Additionally, it protected the brood from pathogenic infection [25]. Glucose oxidase (GOX) is an antiseptic enzyme found in nectar and larval diet, and an additive to prolong the products’ shelf life. In the hypopharyngeal glands, GOX is a catalytic enzyme that catalyzes the conversion of β- d- glucose to gluconic acid and hydrogen peroxide (H2O2) [26] and provides the social immunity. H2O2 functions as an antiseptic, preventing pathogen growth in honeybee larval diet [27].
Owing to the unique reactivity of the immune system to foreign bodies, it provides safety and guarantees the survival of honeybees. The immune system must be strengthened to prevent and control pathogenic viral infections [28]. The maintenance and repair of the immune system are the most costly physiological processes [29]. It has been discovered that nutrition has a significant impact on immunological response [30]. In honeybees, it depends on the type, quality, and diversity of nutrition [31]. It is important to minimize bee stress by (1) providing floral-rich vegetation, (2) minimizing pesticide usage by introducing more organic farming practices, (3) improving existing quarantine measures on bee movements, and (4) effectively monitoring honeybee populations for the development of future management strategies [32]. Herein, we summarized and discussed the effects of different stressors on honeybee immunocompetence, either individually or in combination. Furthermore, we discussed the relationship between nutrition and bee immunity, as nutrition and phytochemicals were discovered to be among the most influential strategies for improving honeybee immunity [33].

3. Main Causes of Honeybee Colony Losses

3.1. Varroa Mite

The ectoparasitic mite V. destructor is considered one of the most important factors behind the recent high annual loss of honeybee colonies. The mite directly damages bees by feeding primarily on honeybee fat body tissue and not hemolymph [34,35]. It has different impacts in different parts of the world, with increased morbidity and colony losses in honeybee colonies in North America, Europe, and Asia. Although this mite has been prevalent in Brazil for many years, no instances of colony losses among Africanized honeybees have been reported [36,37,38].
The physical damage caused by the mite has been reported to suppress the bees’ immune response [39]. Varroa parasitism has inhibited the expression of genes encoding immunity (hymenoptaecin and defensin), longevity, and stem cell proliferation in honeybees [40].
The mite is unlikely to cause the collapse of hives; however, it acts as a vector for a cocktail of viral disease agents, which are among the probable causes for CCD, including the deformed wing virus (DWV), kashmir bee virus, sacbrood virus (SBV), acute bee paralysis virus, and Israeli acute paralysis virus (IAPV) [41,42,43,44].

3.2. Nosema spp.

Nosemosis is a disease that affects honeybees and is caused by intracellular parasites (Nosema apis and Nosema ceranae) that infect the adults’ midgut epithelial cells [45]. N. ceranae infection is highly pathogenic for honeybee colonies, significantly reducing the colony size, brood rearing, and honey production, and increasing winter mortality. In persistent infections, the pathogen can impact colony performance by reducing a colony’s ability to regulate hive temperature or by killing the entire colony [46]. For the European honeybee, N. ceranae reduced homing and orientation skills, and altered the metabolism of forager bees [47].
N. ceranae-infected bees showed changes in the level of ethyl oleate (EO), which is, to date, the only primer pheromone identified in workers that is involved in foraging behavior. Infected bees with high EO titers have a short lifespan [48]. The immune response of bees against N. ceranae comprises the early initiation of AMPs via the Toll and Imd pathways, and the immune response is hampered after seven days of infection [49].

3.3. Viral Pathogens

For honeybees worldwide, over 24 viruses have been discovered, some of which can have major health repercussions [50]. A highly prevalent and relatively virulent virus transmitted by V. destructor which impacts the health of honeybee colonies worldwide is DWV [11]. DWV-induced honeybee loss, coupled with a long-term decline in beekeeping, has become a serious threat to the adequate provision of pollination services, which threatens food security and ecosystem stability [51].
Nitric oxide synthase is produced in high levels of DWV and leads to the formation of interferon-g (IFN-g), which has an inflammatory impact [52]. The Varroa mite can disrupt the dynamics of DWV within the host, turning a cryptic and vertically transmitted virus into a rapidly replicating killer that reaches deadly levels late in the season. The down-regulation of the transcription factor, nuclear factor kappa-B (NF-kB), gene family, is linked to the destabilization of DWV infection [41].
In colonies infected with DWV, V. destructor impacts two immune genes, relish and defensin. Relish up-regulation and defensin down-regulation expression were closely linked to high DWV and mite loads [53]. Additionally, the DWV titer was linked negatively to encapsulation and melanization responses [54]. Contrarily, high titers of DWV alone did not affect the expression of the AMPs and the genes involved in the regulation of melanization [55]. By limiting vitellogenin (Vg) expression, DWV had a favorable impact on the titer, and a negative relationship was observed between the Vg levels and Varroa mite infestation levels [44,56]. Vg is important for bees behavior and development and is linked to energy homeostasis [57].
SBV is a picornavirus in the genus Iflavirus which causes the failure of bee larva to pupate, resulting in the bee’s death [58]. Furthermore, SBV was detected in the hemolymph, ovary, and abdominal shell throughout the growth stages of workers and queens in A. mellifera colonies [59]. It caused the up-regulated expression of AMPs and down-regulated expression of the prophenoloxidase-activating enzyme (PPAE). Additionally, the up-regulation of the expression of putative serpin suppressed the melanization pathway [55].
Israeli acute paralysis virus (IAPV) has been identified as a major cause of CCD [60]; although other studies did not directly associate CCD and the presence of IAPV, successive replication of IAPV was shown to affect the colonies health and thus possibly determine their survival [61,62,63]. In addition, IAPV is a source of infection not only to honeybees, but also bumblebees [64], stingless bees [65], hornets [66], and even ants [67]. IAPV is an RNA virus of honeybees linked to colony losses [68]. IAPV caused immunological signaling abnormalities in adult bees that were more pronounced than in brood. Endocytosis genes, such as Cbl, which is a signal transducer and activator of transcription (STAT), protein inhibitor of activated signal transducer, and hopscotch were up-regulated [68].

3.4. Pesticides

The exposure of honeybees to pesticides compromises their immune responses, navigation ability, learning, and memory [69]. Pesticides in sub-lethal quantities can be harmful to honeybees, as it may not kill bees but reduce their performance and survival during foraging. Bees exposed to pesticides had high vulnerability to infections and hence became means to spread diseases to other parts of the colony or other colonies via the shared use of flowers [9].
Thiamethoxam (TMX), a kind of neonicotinoid, does not promote collapse in healthy colonies in spring. This does not rule out the possibility that colonies will be more vulnerable later in the year, manifested when their capacity to replace lost workers diminishes gradually [70]. In bees infected with Varroa mites, TMX altered the gene expression of their immune systems [71]. Similar changes in immune genes were observed in bees exposed to imidacloprid and infected with Varroa where the potent effect is variation over the three developmental stages (white-eyed pupae, brown-eyed pupae, and newly emerged bees) [72]. The exposure to imidacloprid decreased AMPs in the hemolymph and encapsulation response, owing to the reduction in hemocytes and prophenoloxidase [73].
On the other hand, other studies debated the above notion, demonstrating that neonicotinoids did not negatively influence honeybee colonies and that the honeybee was relatively resistant to neonicotinoid effects in real-world scenarios [74]. These claims were supported by field studies that demonstrated great adaptability of honeybee colonies to environmental challenges, especially when using a sub-lethal dose of neonicotinoids. Equally interesting, clothianidin (CLO) treatment resulted in an increased colony power (the number of brood and adult bees) and a decrease in mortality [74].
Taken together, it was thought that exposure of bees to more than one pesticide can produce a synergistic, antagonistic, or additive effect. Exposure to more than one pesticide agrochemical including pesticides, insecticides, herbicides, and fungicides during field-realistic interaction was synergistically harmful [75].

3.5. Malnutrition

Food resources are collected in large quantities by bee colonies to prepare for scarcity and are stored as honey and bee bread. This is because nutrition deficiency and deterioration can affect development and bee lifespan and increase the likelihood of infestation by a parasite, virus, or disease, resulting in honeybee mortality [76,77]. Bees fed only on water and sugar (low protein diet) exhibited higher mortality and viral load rates, compared with bees fed on higher pollen diets. These results showed that poor nutrition can suppress immunity and that a different host’s nutrition can alter specific components of the immune system [78]. Supplementary nutrition such as homemade sugar syrups can cause undesirable effects on bee health due to the presence of toxic compounds, such as hydroxylmethylfurfural (HMF). In addition, the preparation conditions of these sugar syrups such as temperature or addition of an acidifying substance resulted in a higher amount of HMF and bee mortality [79].
The other threat that may generally affect honeybees health and immune system specificity is GM crops [80]. GM crops are used to produce desired traits, particularly insect and herbicide resistance [81]. GM crops may affect honeybees directly and indirectly. Indirectly, by interfering with volatile chemicals that are efficient for attracting honeybees. The indirect effect is the variations in the quantity and consistency of plant secondary compounds that may cause a deficiency in the main nutrition, which is related to immune system competence [29,33]. Through nutrition, GM can directly suppress insect digestion enzymes, such as amylase and proteases [82]. Accurate data on the direct effect are inadequate, but the fear of this effect exists [83,84]. The available experiments are only performed in the laboratory under artificial conditions, and the observations are based on an unnatural situation. Thus, experiments under natural conditions are greatly required [85].

3.6. Other Causes

Heavy metal pollution originates from various sources. Heavy metals may be ingested by honeybees through water sources and by foraging for nectar and pollen from plants that have already stored heavy metals [86]. Cd, Pb, As, Hg, Ni, and Cr are particularly harmful to living beings due to their high toxicity. Furthermore, elements such as Cu, Fe, Se, Zn, Mn, and Co, which are required for a range of biochemical and physiological processes, can be hazardous to bee colonies [87]. Cd pollution caused significant cellular damage in fat bodies, which was considered to be the cause of a decreased ability to eliminate pathogens [88]. Honeybee microbiomes and metabolomes were impacted [89]. Co, Mn, and Cu presence at xenobiotic levels lowered the phagocytic index and altered the profile of bees’ low-molecular weight proteins [90].
Urbanization is one of the biggest challenges to wild plants and pollinators, including bees [91]. Heavy metals such as Pb and Cd are found in high concentrations in urban areas. In urban areas, bees were more susceptible to disease transmission, particularly the black queen cell virus (BQCV) and fungal pathogen N. ceranae. This effect did not appear to be mediated by immunity, as determined by immune-gene expression, which was not affected by urbanization [90]. Moreover, there was no evidence of immunocompetence differences between managed and feral bees [92].
Nanoparticles (NPs), which are used in a variety of industrial applications, negatively impact human and animal health, including honeybees. CdO or PbO NPs produced histological and cellular abnormalities in honeybee workers’ midgut epithelial cells [93]. When exposed to CdO or PbO NPs, separately or in combination, acetylcholinesterase (AChE) activity and the expression of a variety of stress-related detoxifying enzymes were inhibited. Furthermore, the rate of feeding and survival reduced [94].
The rapid expansion of the telecommunications industry has resulted in a massive increase in the number of mobile phones and the rapid deployment of cell towers across the globe. According to certain studies, honeybees do not rely on the electromagnetic field (EMF) to navigate, and many apiaries that are experiencing losses are in rural areas where cell phone service is absent. The World Health Organization confirmed the same data; however, some researchers revealed that there was standard evidence that the EMF could cause damage in honeybees [95,96]. It was associated with increased bees activity, increased inside temperature, increased queen loss, abnormal real cell production, weight loss, and reduced operculated brood [97]. Chronic radiofrequency EMF exposure significantly reduced the hatching of honeybee queens [98]. In addition, activities related to transport, and artificial water surfaces were thought to be associated with high honeybee colony losses [99].
One proposed reason for honeybee losses was improper beekeeping practices, and it was reported that amateur beekeepers with small beehives and no experience in beekeeping had twice the winter mortality rate than experienced beekeepers [38]. Beekeepers should maintain strong colonies with a young and healthy queen and control the level of Varroa mites by accurately timed and effective control measures. In addition, long-term beekeeping experience is beneficial in reducing winter losses. Mite management should be a top focus for reducing colony losses. Multiyear surveys and surveillance studies are necessary to solve these questions and detect emerging problems [38]. Beekeeper training is warranted to encourage good beekeeping practices and to detect the clinical signs of disease early [12].

4. Interaction between Different Stressors Affects the Bees Immunocompetence

4.1. Interaction between Pesticides and Pathogens

As previously mentioned, many factors including pesticides, diseases, and malnutrition lead to bees’ decline in different regions worldwide. These threats are frequently interconnected, and it is unlikely that colony losses are caused by single stressors (Figure 1, Table 1 and Table 2) [100].
Interactions between pesticides and pathogens may play a role in increased honeybee colony losses, including CCD and other pollinator reductions worldwide [101]. CLO inhibits NF-κB immune signaling in insects at sub-lethal dosages, and CLO and imidacloprid compromise honeybees antiviral defenses regulated by transcription factors [102]. Although other studies estimated that increased pesticides may not always result in increased viral loads [11], exposure to neonicotinoid pesticide imidacloprid, in the presence of the gut parasite N. ceranae, increased the levels of enzymes such as catalase (CAT) and glutathione-S-transferase in the heads of bees. These enzymes are involved in pesticide and parasite resistance to xenobiotics and oxidative stress. Furthermore, stressors affected midgut enzymes, i.e., carboxylesterase alpha (CaE) and carboxylesterase para (CaE p), which are engaged in metabolic and detoxifying processes [101,103,104,105]. In honeybees, the interactions between thiacloprid and N. ceranae caused Nosema to increase, regardless of the thiacloprid dosage [105]. Al Naggar and Bear conducted a series of experiments in which honeybee workers were exposed to sub-lethal field-relevant concentrations of a novel pesticide (Flupyradifurone) for a brief period during their larval development and early adulthood. They tested the long-term effects of a single short exposure to the pesticide and a second ecological stressor later in life in the absence and the presence of the pesticide. They concluded that brief exposure to sub-lethal pesticides during development or early life was sufficient to induce effects later in life, and this could cause a decline in bees health [9].
Imidacloprid and V. destructor played important roles in honeybees population and individual bee survival decline, owing to the inhibition of Vg titer, which modulates bees growth and behavior [57]. When bees were exposed to chronic bee paralysis virus (CBPV) at high imidacloprid doses, the viral load and mortality increased. Low dosages did not influence the viral titer [106]. The effect of TMX on V. destructor-infected bees changed the gene expression in the immune system. Spaetzle, AMPs, abaecin, and defensin-1 were all down-regulated in white infected pupas, while lysozyme-2 was up-regulated. By adding TMX to the Varroa-infested group, the expression of spaetzle, hopscotch, basket, and polyphenol oxidase (PPO) genes was significantly elevated in brown-eyed pupae. Oppositely, TMX did not affect defensin-2 in white- and brown-eyed infested pupae [71].

4.2. Interaction between Pesticides and Poor Nutrition

The combination of low diet and chemical exposure affects bee survival synergistically (−50%). The interaction reduced food consumption (−48%), hemolymph levels of glucose (−60%), and trehalose (−27%) [107]. Researchers have indicated that various insecticides indirectly influence honeybees’ health via diet by suppressing immunity-related genes and negatively altering NFB immunological signaling. It can significantly impair the honeybees’ immune system, reducing the bees antiviral defense regulated by this transcription factor. This may cause direct death or become easy prey to predators [102,108,109]. Bees survival was reduced as a result of the interaction of restricted nectar and nectar availability with neonicotinoid exposures, such as CLO and TMX [107]. Another study estimated the impact of flupyradifurone (FPF) exposure (regarded as bee-friendly, according to standard risk assessment) on poor nutrition where it reduced bee survival, food consumption, flight success, and thermoregulation of honeybees [110].

4.3. Interaction between Pathogens and Poor Nutrition

Nutritional deficiencies increased pathogen load and reduced adult longevity and survival [111]. Diseases altered foraging behavior by reducing foraging abilities or altering floral preferences. In addition, pollination services were impaired when bee populations were reduced or feeding habits were altered [112]. The interaction between poor nutrition and pathogenic infection increased the rate of colony mortality and reduced the ability of bees to fight other stressors [113]. Disease infection (viral, fungal, and bacterial pathogens), reduced bee nutrition (caloric needs, dietary requirements, nutrient storage, gut physiology, and microbiota), and made bees more susceptible to diseases and vice versa [33].

4.4. Interaction between Parasites and Pathogens

The interactions between the DWV and ectoparasitic mite, V. destructor, resulted in DWV replication and increased Varroa reproductive output [114]. V. destructor can vector IAPV in honeybees and are capable of IAPV replication. The density of Varroa mites and the duration of exposure to the mites were positively related to the copy number of IAPV in bees. Furthermore, the mite–virus association may reduce the host immunity, promoting high levels of virus replication. Varroa mites provide a plausible route for IAPV transmission in the field and may significantly contribute to the honeybee diseases associated with CCD [34,62].
Table 1. Summary of laboratory studies discussing the interaction between stressors on honeybees (Apis mellifera L.).
Table 1. Summary of laboratory studies discussing the interaction between stressors on honeybees (Apis mellifera L.).
First StressorSecond StressorModelResultsReferences
Varroa destructorNeonicotinoid insecticidesHoneybees Reduction in survival of long-lived winter honeybees[115]
Deformed wing virus (DWV)White-eye honeybees pupae Higher virus replication[116]
Poor nutrition Freshly emerged honeybee workers Reduction in body weight
Reduction in abdominal protein level
Increased head to abdomen protein ratio
[117]
Nosema ceranaeInsecticide fipronilEmerging honeybees Decreased survival[118]
DWVNewly emerged honeybee workers Higher virus replication in infected bees in a dose- and nutrition-dependent manner[119]
Neurotoxic insecticidesEmerging honeybees Increased mortality
of immunity-related genes
Strong alteration of midgut immunity
[104]
ThiaclopridFreshly emerged honeybee workers Higher Nosema replication[105]
Microsporidia NosemaNeonicotinoid (imidacloprid)Young Africanized honeybees Higher mortality rate
Higher pathogen load
[120]
ThiamethoxamN. ceranaeLarvae and adult honeybees Gene expression patterns change with time in each treatment[121]
Chronic bee paralysis virus (CBPV)Nine-day-old bees Higher viral titers
Increased mortality
[122]
CBPVEmerging honeybees High pesticides increased mortality without an increase in viral titers
Low pesticide has no effect on mortality, however, increases in viral titers
[123]
ImidaclopridN. ceranaeHoneybee queens Decreased metabolic and detoxification functions
Increased mortality
Reduced lifespan
[103]
N. ceranaeHoneybees Higher Nosema infection load
Increased mortality of honey bee colonies
[101]
ThiaclopridMicrosporidian N. ceranae
and BQCV
Larval and adult honeybees Elevation of viral load
Increased individual mortality
[124]
ClothianidinNosema spp.Emerging honeybees No any synergistic effect[125]
Fipronil and ThiaclopridN. ceranaeEmerging honeybees Higher Nosema infection
Higher mortality
[126]
Poor nutritionIsraeli acute paralysis virus (IAPV).HoneybeesElevation of bee mortality[113]
Table 2. Summary of field studies discussing the interaction between stressors on honeybees (Apis mellifera L.).
Table 2. Summary of field studies discussing the interaction between stressors on honeybees (Apis mellifera L.).
First StressorSecond StressorModelResultsReferences
Varroa destructorClothianidinHoneybeesReduced weight and number
Up-regulated differentially expressed genes (DEGs) associated with metabolism
[127]
Deformed wing virus (DWV)Africanized honeybeesInhibition of immunity
Reduction in lifespan
[128]
Neonicotinoid insecticide imidaclopridHoneybeesReduce homing success of foragers
High V. destructor load
[129]
Poor nutrition Freshly emerged honeybee workersDeath of bee about 40%
Ageing enhancement
[117]
Viruses (Acute-Kashmir-Israeli and DWV,
acaricide)
HoneybeesHigher virus replication
immune-suppression
[130]
DWVHoneybeesDown-regulation of a member of the NF-Κβ
Increase in bees mortality
[41]
NosemaHerbicide glyphosate and the fungicide difenoconazoleEmerging honeybeesInduces strong physiological disturbances
Reduced honeybees longevity
[131]
Nosema apisNeonicotinoid pesticide
Thiamethoxam
Honeybee workersIncrease in mortality
Reduction in immunocompetence
[132]
V.
destructor, Nosema spp.
ImidaclopridHoneybeesReduced the flight performance by ~24%
No effect on colony size
[133]
AcaricidesN. ceranaeNewly emerged
honeybees
Reduction in ethyl oleate as primer pheromone[134]
ParasitesPesticidesHoneybees Increased mortality[135]
ImidaclopridCBPVAdult honeybee workersHigher virus load and mortality in case of higher doses
Lower dosages had no influence on virus titer
[106]
ClothianidinVarroaHoneybeesNo elevation of immune gene expression [74]
DWVHoneybeesDecreased immunocompetence expression
Higher replication of the DWV
[102]
Pathogens
(RNA viruses, DNA virus, Nosema SP, and beneficial bacteria)
BumblebeesNo increase in viral titers
Impairs reproduction of queens and males
[136]
Pathogens Honeybees No adverse effect on honey bee colonies
No increase in pathogens titers
[137]
Infection with parasites and diseasesHoneybees No increase in titers of several viruses
No impact on success of colony or honey yield
[138]
RoundupVRNosema microsporidiaEmerged and adult honeybeesReduced survival rate and increased food consumption of the bees[139]
ThiamethoxamN. ceranaeApis mellifera carnicaEpithelium degeneration
Higher mortality
[140]
N. ceranaeLarvae and adult honeybeesHighest mortality rate
Decreased immunocompetence expression
[121]
DWVNewly emerged beesThe chance of not returning to the hive after the first flight was raised
Decreased survival
[141]
Chronic bee paralysis virus (CBPV)Emerging honeybeesHigh pesticides increased mortality without an increase in viral titers
Low pesticide has no effect on mortality but increases in viral titers
[123]
CBPVAdult honeybee workersHigher viral titers
Increased mortality
[122]
Neonicotinoid insecticides V. destructorNewly emerged beesDecreased immunocompetence expression [142]
Insecticide Flupyradifurone (FPF, Sivanto®)Nutritional stressForaging honeybeesReduced bee survival and food consumption[110]
Pesticides (fipronil, thiamethoxam and boscalid)N. ceranaeNewly emerged honeybees Gut microbiota dysbiosis[143]
Neonicotinoid pesticidesNutritional stressHoneybeesReduction in bee survival
Reduction in food consumption
[107]
Pesticides (dimethoate, clothianidin and fluvalinate)American foulbrood (AFB)Honeybees Higher mortality
Reduction in hemocyte counts
[144]
Poor nutritionVirus infectionHoneybeesElevation of bee mortality[113]
ThiamethoxamBumblebees micro-coloniesSlower growth
Reduced reproductive efforts
[145]
ThiamethoxamApis mellifera ligusticaNegative impact on hypopharyngeal gland development[146]

5. Strategies to Enhance Honeybee Immunity

5.1. Fortified Nutrients

Currently, honeybees face numerous threats that hinder their survival. Special attention should be paid to beekeepers, bee supplements, and nutrition to limit the risk of viruses, other diseases, and agrochemicals. Beekeepers should support colonies with suitable supplementary feeding during dearth periods [147]. In addition, the diversity of nutrition that comes from different natural plant sources can improve honeybee immunity, antiviral, and antimicrobial properties [33]. A diet with pollen from different plants or high-quality single pollen organs can enhance honeybees’ immunity and survival as shown in Figure 2.
Using a mixed pollen diet of three pollen species indirectly increased bee larvae immunocompetence and resistance to fungal diseases, such as Aspergillus fumigatus [111]. Experiments on two different groups of honeybees correlated with these findings. The first group exclusively ate clover pollen, while the second ate clover and partridge pea (Chamaecrista fasciculate) pollen. In the absence of the pathogen, they exhibited no change in mortality, however, when the virus was administered, they showed a significant difference. When honeybees were infected by a virus, a combination of clover and partridge pea significantly reduced mortality and enhanced immunity and viral resistance [148]. Di Pasquale estimated that young nurse bees were affected by pollen quality, not multiflora pollen [31]
Furthermore, protein nutrition is the key factor to improve the immunity of honeybees and support the survival of honeybee communities [141]. For Nosema infection, the availability of various floral resources can increase infection tolerance and complement the limited influence of particular pollen [149]. Nevertheless, a monofloral diet may occasionally reduce the mortality of honeybees, compared with that of bees denied pollen [150]. Nutritional stress associated with the monoculture and consumption of monofloral pollen affected bee gut microbiota and immunity and increased pathogen infection, such as N. ceranae. Under laboratory conditions, honeybees fed with the monofloral pollen of Eucalyptus grandis exhibited less gut microbiota and reduced gene immunity compared with those of honeybees fed with multifloral pollen [151].
Honeybee food supplements can boost the health of colonies and minimize the impact of stressors during pollen foraging unavailable periods [152]. Artificial food supplements using fresh and dry Cyanobacteria, Arthrospira platensis, exhibited a marked overlap in proteome expression patterns and similar dietary protein absorption, similar to natural pollen [153]. Chlorella sorokiniana played a role in bees development via increased fat deposition, Vg transcript levels, decreased target of rapamycin, and InR2 transcript levels [154].
Other marine organisms such as seaweeds used in the production of Hive Alive reduced N. ceranae spores and increased the number of workers [155]. When bacteria-like bifidobacteria and lactobacilli were added to sugar syrup, the area of pollen storage and harvestable honey dramatically increased. It promoted the growth of Acetobacteraceae and Bifidobacterium spp, which are important for bees nutrition [156].
The role of dietary phytochemicals in honeybees’ sensitivity to pesticide exposure cannot be overstated. The dietary supplementation with p-coumaric and indole-3-acetic acids (20 μM) enhanced the survival of bees exposed to tau-fluvalinate (~20%) [157]. Abscisic acid (ABA), a natural component found in nectar, honey, pollen, and honeybees, is critical for bees’ health. In the dietary strategies tested, ABA supplementation positively impacted the population dynamics of A. mellifera colonies during overwintering and nosemosis at the colony level (prevalence) [158]. Most protein supplements are made from high-protein foods such as soy, yeast, or natural pollen, such as MegaBee®, Feed-Bee®, Bee-Pro®, Global Patties®, and Ultra Bee® [159]. Non-protein amino acids such as gamma-aminobutyric acid and beta-alanine were used to reduce the possibility of beneficial microbiota imbalance following antivarroa and antinosemosis therapy [160]. Artificial protein supplements such as Beewell Aminoplus boosted bee survivability, decreased Nosema spore levels, had an immunostimulatory impact, and increased the antioxidative protection of the bees against N. ceranae [161,162]. Another study estimated that colonies fed on pollen had lower titers of BQCV and Nosema compared with colonies fed on protein supplements, such as Bee-ProV [163]. In addition, FeedBeeVR did not affect queen development compared with a sugar-based diet supplemented with honey and fresh pollen [164]. The supplementation of honeybees with inadequately chosen probiotics or both probiotics and prebiotics cannot prevent the development of Nosemosis but can deregulate insect immune systems, which may result in considerable bee mortality [165].

5.2. Natural Products as Alternative Sources

The high cost of chemical treatments and the risk of toxic residues presence in bee products pose problems [166]. The existing treatments may only kill some mites, leaving them more resistant to breed in the next generation, thereby increasing their resistance over time [167]. As a result, scientists worldwide are working to develop effective medicines that have minimal side effects on bee products.
Natural products are one of the sources of these treatments. Essential oils such as thymol, linalool, and camphor, as well as cocktails of thymol, eucalyptol, menthol, and others, have been confirmed to be particularly efficient in suppressing Varroa mites. These types of essential oils were discovered to lower mortality rates among bees in diseased colonies [168]. Although natural products therapy has fewer side effects than chemical therapy, the efficacy of these substances varies depending on the climate and colony condition [169].
Recently, Chinese herbal medicine has demonstrated a unique antiviral effect for both human and animal life. Honeybees are at risk from SBV and Chinese sacbrood virus (CSBV). Infected larvae will not develop into pupae and will eventually die, and there is currently no effective cure for the virus [20]. Radix isatidis, a Chinese herbal remedy, was primarily utilized to treat human influenza viruses. It has recently been proved to effectively regulate CSBV by suppressing its replication, increasing immunological response, and extending the lifespan of CSBV infection larvae, thereby lowering death rates and preventing CCD [170]. DWV and Lake Sinai virus are two RNA viruses with positive strands that kill honeybees. Bees fed with polypore mushroom extracts exhibited a strong ability to diminish both virus larvae. Modified porphyrins, which are mostly produced by living organisms, can reduce spore burdens in bees and increase the survival likelihood of bees infected with RNA viruses [171].
Essential oils and extracts of tea tree oil NPs exhibited an extremely high antibacterial effect against AFB and European foulbrood (EFB) in vivo. They inhibited the growth of AFB and EFB at low concentrations; this had a high effect on the survival of the colony [172]. Nosemosis is one of the most widespread diseases among honeybee colonies. It is mainly caused by the fungal microsporidian parasites N. apis and N. ceranae, which can cause honeybee losses. The anti-fungal agent, fumagillin, is the most common treatment for nosemosis. However, the causative agents may acquire treatment resistance, which could pose a threat in the future [173]. Natural products are used as an alternative treatment. Cryptocarya alba essential oils and monoterpenes have been demonstrated to possess potent anti-fungal properties against Nosemosis. They can slow and stop the spread of disease, thereby increasing the survival chances of the colony [174]. N. ceranae was treated with ApiHerbfi, a nutritional supplement, and Api-Bioxalfi, a veterinary drug, and the infections were reduced substantially [175]. Furthermore, glucosinolates derived of Brassica nigra and Eruca sativa were used, and hence N. ceranae was inhibited in an in vitro model [176]. However, in the field trials, the treatments had no significant effects on colonies development or bees mortality when compared to the negative controls, and the treatments had no effect on the prevalence of N. ceranae infected bees in both pre- and post-treatment samples, so further optimization of the dose or application methods is needed [177].

5.3. Nanomaterials as Novel Alternative Approaches

Nanotechnology is one of the most active areas in research that has proven to be extremely versatile and has sparked a revolution in medical treatments, fast diagnoses, cellular regeneration, and medication delivery [178,179]. It has been employed to discover novel therapies for honeybee diseases, as current antibiotics do not entirely eradicate the infection. Antibiotic use over time results in an accumulation of antibiotics in honey, which can be hazardous to human health [180]. Furthermore, it is damaging to the gut microbiota of bees, impairing their metabolism, which results in weak immunity, high disease risk, and short bee lifespans [181]. As a result, through ultraviolet–visible (UV–VIS) spectrophotometry and scanning electron microscopy, researchers discovered that camphor tree silver NPs could positively regulate the isolated bacterial pathogens of AFB and EFB [182]. Similarly, tea tree oil NPs have been utilized in other studies to treat or prevent AFB and EFB due to their high efficacy against Paenibacillus sp. and M. plutonius strains, respectively, which are the causal agents [172]. AgNPs have anti-microsporidian activity and could be effective components of formulations for treating or preventing microsporidia Nosema bombycis [183]. However, additional research is needed on this topic in order to develop nanoparticle treatments that will reduce bee diseases while having no negative impact on honeybee health.

5.4. Organizations and Initiatives Directed to Saving the Bees

Organizations and initiatives are directed to save the bees in response to honeybee colony losses. Working groups such as COLOSS, a COST initiative funded by the EU Science Foundation, have been formed to address the global loss of managed honeybee colonies. By offering strategies to reduce the risk of this problem, COLOSS is playing an important role in identifying and mitigating colony losses [184]. One of these strategies was adequate nutrition that was a key factor for honeybees’ growth and colony development. Several studies show that the nutritional quality of diet is directly proportional to the ability of bees to face challenges or stressors [185]. However, diverse feeding regimes are used by beekeepers all throughout the world, particularly during the winter season, and these fluctuate from nation to nation and beekeeper to beekeeper. For example, in China, which has a large number of managed honeybee colonies, beekeepers feed winter bees with honeycombs or sugar [186]. In Egypt, colonies are supplied with artificial diet cake and syrup supplemented with vitamin C; this combination has a significant impact on colonies’ growth compared to sugar syrup only [187]. The feeding regime in Ethiopia is honey and water and shiro (roasted spiced pulses flour) to overcome the feed shortage in the dry season [188]. Apiary management in most nations necessitates an initial feeding of carbohydrate and protein. Protein is not always used; in the spring, a carbohydrate such as sucrose syrup or high corn syrup can be used to replicate nectar flow and enhance brood raising. This extra feed is utilized in the fall to increase fructose storage for the winter [189]. As a result, frequent COLOSS nutrition task force meetings could serve to protect bees from varied stressors, particularly during the winter seasons, by exchanging different apiary management protocols and feeding regimes used in different regions of the world.

6. Conclusions

Honeybees are important pollinators for humans and ecosystems. Unfortunately, CCD, a serious threat to the beekeeping industry, has recently been reported worldwide. It is caused by a variety of stressors that affect the immune system of bees, such as pathogens, insecticides, and inadequate diets. Scholars and governments have universally agreed that there is no single cause is to be blamed and that the causes are interconnected. However, further research is required to understand the mechanisms behind the interactions among different stressors and to discover more important genes and signaling pathways involved in honeybee stress responses. First, beekeepers must consider these aspects by planting floral-rich vegetation around the apiary and using proper dietary supplements. Second, experts could agree on a scientific plan for the treatment and management of the related diseases and pests, including the development of new nanotechnology-based remedies. Finally, organizations and stakeholders should pay attention to training to improve the efficiency of breeders and recent graduates in apiary management.

Author Contributions

Conceptualization, H.R.E.-S.; validation, H.R.E.-S. and S.A.M.K.; writing—original draft preparation, H.R.A., A.A.A.E.-W., and Y.A.N.; writing—review and editing, S.A.M.K., A.S., A.F.A., N.F.A., Z.G., S.G.M., A.K., S.M.A., K.W., and H.R.E.-S.; supervision, H.R.E.-S.; and funding acquisition, H.R.E.-S. All authors have read and agreed to the published version of the manuscript.

Funding

This work was supported by National Natural Science Foundation of China (32172791).

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Acknowledgments

Kai Wang also gratefully acknowledged the financial support from the National Natural Science Foundation of China. #Dedicated with great pleasure and honor to Rob Verpoorte, Leiden University, Netherland on the occasion of his 75th birthday.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Stein, K.; Coulibaly, D.; Stenchly, K.; Goetze, D.; Porembski, S.; Lindner, A.; Konaté, S.; Linsenmair, E.K. Bee pollination increases yield quantity and quality of cash crops in Burkina Faso, West Africa. Sci. Rep. 2017, 7, 17691–17700. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  2. Khalifa, S.A.M.; Elshafiey, E.H.; Shetaia, A.A.; El-Wahed, A.A.A.; Algethami, A.F.; Musharraf, S.G.; Alajmi, M.F.; Zhao, C.; Masry, S.H.D.; Abdel-Daim, M.M.; et al. Overview of bee pollination and its economic value for crop production. Insects 2021, 12, 688. [Google Scholar] [CrossRef] [PubMed]
  3. Klein, A.M.; Vaissière, B.E.; Cane, J.H.; Steffan-Dewenter, I.; Cunningham, S.A.; Kremen, C.; Tscharntke, T. Importance of pollinators in changing landscapes for world crops. Proc. R. Soc. B Biol. Sci. 2007, 274, 303–313. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  4. Hristov, P.; Neov, B.; Shumkova, R.; Palova, N. Significance of apoidea as main pollinators. Ecological and economic impact and implications for human nutrition. Diversity 2020, 12, 280. [Google Scholar] [CrossRef]
  5. Dicks, L.V.; Breeze, T.D.; Ngo, H.T.; Senapathi, D.; An, J.; Aizen, M.A.; Basu, P.; Buchori, D.; Galetto, L.; Garibaldi, L.A.; et al. A global-scale expert assessment of drivers and risks associated with pollinator decline. Nat. Ecol. Evol. 2021, 5, 1453–1461. [Google Scholar] [CrossRef]
  6. Goodrich, B.K. Do more bees imply higher fees? Honey bee colony strength as a determinant of almond pollination fees. Food Policy 2019, 83, 150–160. [Google Scholar] [CrossRef]
  7. VanEngelsdorp, D.; Traynor, K.S.; Andree, M.; Lichtenberg, E.M.; Chen, Y.; Saegerman, C.; Cox-Foster, D.L. Colony collapse disorder (CCD) and bee age impact honey bee pathophysiology. PLoS ONE 2017, 12, e0179535. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  8. van Engelsdorp, D.; Meixner, M.D. A historical review of managed honey bee populations in Europe and the United States and the factors that may affect them. J. Invertebr. Pathol. 2010, 103, S80–S95. [Google Scholar] [CrossRef]
  9. Al Naggar, Y.; Baer, B. Consequences of a short time exposure to a sublethal dose of Flupyradifurone (Sivanto) pesticide early in life on survival and immunity in the honeybee (Apis mellifera). Sci. Rep. 2019, 9, 19753–19762. [Google Scholar] [CrossRef] [Green Version]
  10. Al Naggar, Y.; Paxton, R.J. Mode of transmission determines the virulence of black queen cell virus in adult honey bees, posing a future threat to bees and apiculture. Viruses 2020, 12, 535. [Google Scholar] [CrossRef]
  11. Al Naggar, Y.; Paxton, R.J. The novel insecticides flupyradifurone and sulfoxaflor do not act synergistically with viral pathogens in reducing honey bee (Apis mellifera) survival but sulfoxaflor modulates host immunocompetence. Microb. Biotechnol. 2021, 14, 227–240. [Google Scholar] [CrossRef] [PubMed]
  12. Jacques, A.; Laurent, M.; Consortium, E.; Ribière-Chabert, M.; Saussac, M.; Bougeard, S.; Budge, G.E.; Hendrikx, P.; Chauzat, M.-P. A pan-European epidemiological study reveals honey bee colony survival depends on beekeeper education and disease control. PLoS ONE 2017, 12, e0172591. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  13. Mullapudi, E.; Přidal, A.; Pálková, L.; de Miranda, J.R.; Plevka, P. Virion structure of Israeli acute bee paralysis virus. J. Virol. 2016, 90, 8150–8159. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  14. van Engelsdorp, D.; Evans, J.D.; Saegerman, C.; Mullin, C.; Haubruge, E.; Nguyen, B.K.; Frazier, M.; Frazier, J.; Cox-Foster, D.; Chen, Y.; et al. Colony collapse disorder: A descriptive study. PLoS ONE 2009, 4, e6481. [Google Scholar] [CrossRef]
  15. Nazzi, F.; Annoscia, D.; Caprio, E.; Di Prisco, G.; Pennacchio, F. Honeybee immunity and colony losses. Entomologia 2014, 2, 80–87. [Google Scholar] [CrossRef] [Green Version]
  16. Antúnez, K.; Martín-Hernández, R.; Prieto, L.; Meana, A.; Zunino, P.; Higes, M. Immune suppression in the honey bee (Apis mellifera) following infection by Nosema ceranae (Microsporidia). Environ. Microbiol. 2009, 11, 2284–2290. [Google Scholar] [CrossRef]
  17. Fallon, J.P.; Troy, N.; Kavanagh, K. Pre-exposure of Galleria mellonella larvae to different doses of Aspergillus fumigatus conidia causes differential activation of cellular and humoral immune responses. Virulence 2011, 2, 413–421. [Google Scholar] [CrossRef] [Green Version]
  18. DeGrandi-Hoffman, G.; Chen, Y. Nutrition, immunity and viral infections in honey bees. Curr. Opin. Insect Sci. 2015, 10, 170–176. [Google Scholar] [CrossRef] [Green Version]
  19. Karlikow, M.; Goic, B.; Saleh, M.-C. RNAi and antiviral defense in Drosophila: Setting up a systemic immune response. Dev. Comp. Immunol. 2014, 42, 85–92. [Google Scholar] [CrossRef] [Green Version]
  20. Brutscher, L.M.; Flenniken, M.L. RNAi and antiviral defense in the honey bee. J. Immunol. Res. 2015, 2015, 941897. [Google Scholar] [CrossRef] [Green Version]
  21. Vung, N.N.; Choi, Y.S.; Kim, I. High resistance to Sacbrood virus disease in Apis cerana (Hymenoptera: Apidae) colonies selected for superior brood viability and hygienic behavior. Apidologie 2020, 51, 61–74. [Google Scholar] [CrossRef]
  22. Goblirsch, M.; Warner, J.F.; Sommerfeldt, B.A.; Spivak, M. Social fever or general immune response? Revisiting an example of social immunity in honey bees. Insects 2020, 11, 528. [Google Scholar] [CrossRef] [PubMed]
  23. Cini, A.; Bordoni, A.; Cappa, F.; Petrocelli, I.; Pitzalis, M.; Iovinella, I.; Dani, F.R.; Turillazzi, S.; Cervo, R. Increased immunocompetence and network centrality of allogroomer workers suggest a link between individual and social immunity in honeybees. Sci. Rep. 2020, 10, 8928–8939. [Google Scholar] [CrossRef] [PubMed]
  24. Simone, M.; Evans, J.D.; Spivak, M. Resin collection and social immunity in honey bees. Evol. Int. J. Org. Evol. 2009, 63, 3016–3022. [Google Scholar] [CrossRef] [PubMed]
  25. Borba, R.S.; Spivak, M. Propolis envelope in Apis mellifera colonies supports honey bees against the pathogen, Paenibacillus larvae. Sci. Rep. 2017, 7, 11429–11440. [Google Scholar] [CrossRef] [Green Version]
  26. Bucekova, M.; Valachova, I.; Kohutova, L.; Prochazka, E.; Klaudiny, J.; Majtan, J. Honeybee glucose oxidase—its expression in honeybee workers and comparative analyses of its content and H2O2-mediated antibacterial activity in natural honeys. Naturwissenschaften 2014, 101, 661–670. [Google Scholar] [CrossRef]
  27. Brudzynski, K. Effect of hydrogen peroxide on antibacterial activities of Canadian honeys. Can. J. Microbiol. 2006, 52, 1228–1237. [Google Scholar] [CrossRef]
  28. Alkhatib, A. Antiviral functional foods and exercise lifestyle prevention of coronavirus. Nutrients 2020, 12, 2633. [Google Scholar] [CrossRef]
  29. Roger, N.; Michez, D.; Wattiez, R.; Sheridan, C.; Vanderplanck, M. Diet effects on bumblebee health. J. Insect Physiol. 2017, 96, 128–133. [Google Scholar] [CrossRef]
  30. Aronstein, K.A.; Saldivar, E.; Vega, R.; Westmiller, S.; Douglas, A.E. How Varroa parasitism affects the immunological and nutritional status of the honey bee, Apis mellifera. Insects 2012, 3, 601–615. [Google Scholar] [CrossRef] [Green Version]
  31. Di Pasquale, G.; Salignon, M.; Le Conte, Y.; Belzunces, L.P.; Decourtye, A.; Kretzschmar, A.; Suchail, S.; Brunet, J.-L.; Alaux, C. Influence of pollen nutrition on honey bee health: Do pollen quality and diversity matter? PLoS ONE 2013, 8, e72016. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  32. Goulson, D.; Nicholls, E.; Botías, C.; Rotheray, E.L. Bee declines driven by combined stress from parasites, pesticides, and lack of flowers. Science 2015, 347, 1255957. [Google Scholar] [CrossRef] [PubMed]
  33. Dolezal, A.G.; Toth, A.L. Feedbacks between nutrition and disease in honey bee health. Curr. Opin. Insect Sci. 2018, 26, 114–119. [Google Scholar] [CrossRef]
  34. Gebremedhn, H.; Amssalu, B.; De Smet, L.; De Graaf, D.C. Factors restraining the population growth of Varroa destructor in Ethiopian honey bees (Apis mellifera simensis). PLoS ONE 2019, 14, e0223236. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  35. Ramsey, S.D.; Ochoa, R.; Bauchan, G.; Gulbronson, C.; Mowery, J.D.; Cohen, A.; Lim, D.; Joklik, J.; Cicero, J.M.; Ellis, J.D.; et al. Varroa destructor feeds primarily on honey bee fat body tissue and not hemolymph. Proc. Natl. Acad. Sci. USA 2019, 116, 1792–1801. [Google Scholar] [CrossRef] [Green Version]
  36. De Figueiró Santos, J.; Coelho, F.C.; Bliman, P.A. Behavioral modulation of infestation by varroa destructor in bee colonies. Implications for colony stability. PLoS ONE 2016, 11, e0160465. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  37. González-Cabrera, J.; Bumann, H.; Rodríguez-Vargas, S.; Kennedy, P.J.; Krieger, K.; Altreuther, G.; Hertel, A.; Hertlein, G.; Nauen, R.; Williamson, M.S. A single mutation is driving resistance to pyrethroids in European populations of the parasitic mite, Varroa destructor. J. Pest Sci. 2018, 91, 1137–1144. [Google Scholar] [CrossRef]
  38. Morawetz, L.; Köglberger, H.; Griesbacher, A.; Derakhshifar, I.; Crailsheim, K.; Brodschneider, R.; Moosbeckhofer, R. Health status of honey bee colonies (Apis mellifera) and disease-related risk factors for colony losses in Austria. PLoS ONE 2019, 14, e0219293. [Google Scholar] [CrossRef]
  39. Richards, E.H.; Jones, B.; Bowman, A. Salivary secretions from the honeybee mite, Varroa destructor: Effects on insect haemocytes and preliminary biochemical characterization. Parasitology 2011, 138, 602–608. [Google Scholar] [CrossRef] [Green Version]
  40. Koleoglu, G.; Goodwin, P.H.; Reyes-Quintana, M.; Guzman-Novoa, E. Effect of Varroa destructor, counding and Varroa homogenate on gene expression in brood and adult honey bees. PLoS ONE 2017, 12, e0169669. [Google Scholar] [CrossRef] [Green Version]
  41. Nazzi, F.; Brown, S.P.; Annoscia, D.; Del Piccolo, F.; Di Prisco, G.; Varricchio, P.; Della Vedova, G.; Cattonaro, F.; Caprio, E.; Pennacchio, F. Synergistic parasite-pathogen interactions mediated by host immunity can drive the collapse of honeybee colonies. PLoS Pathog. 2012, 8, e1002735. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  42. Kielmanowicz, M.G.; Inberg, A.; Lerner, I.M.; Golani, Y.; Brown, N.; Turner, C.L.; Hayes, G.J.R.; Ballam, J.M. Prospective large-scale field study generates predictive model identifying major contributors to colony losses. PLoS Pathog. 2015, 11, e1004816. [Google Scholar] [CrossRef] [Green Version]
  43. Di Prisco, G.; Pennacchio, F.; Caprio, E.; Boncristiani, H.F.; Evans, J.D.; Chen, Y. Varroa destructor is an effective vector of Israeli acute paralysis virus in the honeybee, Apis mellifera. J. Gen. Virol. 2011, 92, 151–155. [Google Scholar] [CrossRef] [PubMed]
  44. Dainat, B.; Evans, J.D.; Chen, Y.P.; Gauthier, L.; Neumann, P. Predictive markers of honey bee colony collapse. PLoS ONE 2012, 7, e32151. [Google Scholar] [CrossRef] [PubMed]
  45. Gisder, S.; Schüler, V.; Horchler, L.L.; Groth, D.; Genersch, E. Long-term temporal trends of Nosema spp. infection prevalence in Northeast Germany: Continuous spread of Nosema ceranae, an emerging pathogen of honey bees (Apis mellifera), but no general replacement of Nosema apis. Front. Cell. Infect. Microbiol. 2017, 7, 301–314. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  46. Higes, M.; Martín-Hernández, R.; Botías, C.; Bailón, E.G.; González-Porto, A.V.; Barrios, L.; Del Nozal, M.J.; Bernal, J.L.; Jiménez, J.J.; Palencia, P.G.; et al. How natural infection by Nosema ceranae causes honeybee colony collapse. Environ. Microbiol. 2008, 10, 2659–2669. [Google Scholar] [CrossRef] [PubMed]
  47. Dosselli, R.; Grassl, J.; Carson, A.; Simmons, L.W.; Baer, B. Flight behaviour of honey bee (Apis mellifera) workers is altered by initial infections of the fungal parasite Nosema apis. Sci. Rep. 2016, 6, 36649–36659. [Google Scholar] [CrossRef] [Green Version]
  48. Dussaubat, C.; Maisonnasse, A.; Crauser, D.; Beslay, D.; Costagliola, G.; Soubeyrand, S.; Kretzchmar, A.; Le Conte, Y. Flight behavior and pheromone changes associated to Nosema ceranae infection of honey bee workers (Apis mellifera) in field conditions. J. Invertebr. Pathol. 2013, 113, 42–51. [Google Scholar] [CrossRef]
  49. Li, W.; Evans, J.D.; Li, J.; Su, S.; Hamilton, M.; Chen, Y. Spore load and immune response of honey bees naturally infected by Nosema ceranae. Parasitol. Res. 2017, 116, 3265–3274. [Google Scholar] [CrossRef]
  50. Grozinger, C.M.; Flenniken, M.L. Bee viruses: Ecology, pathogenicity, and impacts. Annu. Rev. Entomol. 2019, 64, 205–226. [Google Scholar] [CrossRef]
  51. Škubnik, K.; Nováček, J.; Füzik, T.; Přidal, A.; Paxton, R.J.; Plevka, P. Structure of deformed wing virus, a major honey bee pathogen. Proc. Natl. Acad. Sci. USA 2017, 114, 3210–3215. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  52. Quintana, S.; Brasesco, C.; Negri, P.; Marin, M.; Pagnuco, I.; Szawarski, N.; Reynaldi, F.; Larsen, A.; Eguaras, M.; Maggi, M. Up-regulated pathways in response to Deformed Wing Virus infection in Apis mellifera (Hymenoptera: Apidae). Rev. Soc. Entomol. Argent. 2019, 78, 1–11. [Google Scholar] [CrossRef] [Green Version]
  53. Barroso-Arévalo, S.; Vicente-Rubiano, M.; Puerta, F.; Molero, F.; Sánchez-Vizcaíno, J.M. Immune related genes as markers for monitoring health status of honey bee colonies. BMC Vet. Res. 2019, 15, 72–86. [Google Scholar] [CrossRef] [Green Version]
  54. Di, G.; Annoscia, D.; Margiotta, M.; Ferrara, R.; Varricchio, P.; Zanni, V. A mutualistic symbiosis between a parasitic mite and a pathogenic virus undermines honey bee immunity and health. Proc. Natl. Acad. Sci. USA 2016, 113, 3203–3208. [Google Scholar] [CrossRef] [Green Version]
  55. Ryabov, E.V.; Fannon, J.M.; Moore, J.D.; Wood, G.R.; Evans, D.J. The iflaviruses sacbrood virus and deformed wing virus evoke different transcriptional responses in the honeybee which may facilitate their horizontal or vertical transmission. PeerJ 2016, 4, e1591. [Google Scholar] [CrossRef] [Green Version]
  56. Smart, M.; Pettis, J.; Rice, N.; Browning, Z.; Spivak, M. Linking measures of colony and individual honey bee health to survival among apiaries exposed to varying agricultural land use. PLoS ONE 2016, 11, e0152685. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  57. Abbo, P.M.; Kawasaki, J.K.; Hamilton, M.; Cook, S.C.; DeGrandi-Hoffman, G.; Li, W.F.; Liu, J.; Chen, Y.P. Effects of Imidacloprid and Varroa destructor on survival and health of European honey bees, Apis mellifera. Insect Sci. 2017, 24, 467–477. [Google Scholar] [CrossRef] [Green Version]
  58. Li, J.; Huang, S.; Heerman, M.; Rodr, C.; Banmeke, O.; Brister, J.R.; Hatcher, E.L.; Cao, L.; Hamilton, M.; Chen, Y. The phylogeny and pathogenesis of sacbrood virus (SBV) infection in european honey bees, Apis mellifera. Viruses 2019, 11, 61. [Google Scholar] [CrossRef] [Green Version]
  59. Shan, L.; Liuhao, W.; Jun, G.; Yujie, T.; Yanping, C.; Jie, W.; Jilian, L. Chinese Sacbrood virus infection in Asian honey bees (Apis cerana cerana) and host immune responses to the virus infection. J. Invertebr. Pathol. 2017, 150, 63–69. [Google Scholar] [CrossRef]
  60. Cox-Foster, D.L.; Conlan, S.; Holmes, E.C.; Palacios, G.; Evans, J.D.; Moran, N.A.; Quan, P.L.; Briese, T.; Hornig, M.; Geiser, D.M.; et al. A metagenomic survey of microbes in honey bee colony collapse disorder. Science 2007, 318, 283–287. [Google Scholar] [CrossRef] [Green Version]
  61. Johnson, R.M.; Evans, J.D.; Robinson, G.E.; Berenbaum, M.R. Changes in transcript abundance relating to colony collapse disorder in honey bees (Apis mellifera). Proc. Natl. Acad. Sci. USA 2009, 106, 14790–14795. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  62. Hou, C.; Rivkin, H.; Slabezki, Y.; Chejanovsky, N. Dynamics of the presence of israeli acute paralysis virus in honey bee colonies with colony collapse disorder. Viruses 2014, 6, 2012–2027. [Google Scholar] [CrossRef] [Green Version]
  63. Cornman, R.S.; Tarpy, D.R.; Chen, Y.; Jeffreys, L.; Lopez, D.; Pettis, J.S.; VanEngelsdorp, D.; Evans, J.D. Pathogen webs in collapsing honey bee colonies. PLoS ONE 2012, 7, e43562. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  64. Meeus, I.; de Miranda, J.R.; de Graaf, D.C.; Wäckers, F.; Smagghe, G. Effect of oral infection with Kashmir bee virus and Israeli acute paralysis virus on bumblebee (Bombus terrestris) reproductive success. J. Invertebr. Pathol. 2014, 121, 64–69. [Google Scholar] [CrossRef] [Green Version]
  65. Alvarez, L.J.; Reynaldi, F.J.; Ramello, P.J.; Garcia, M.L.G.; Sguazza, G.H.; Abrahamovich, A.H.; Lucia, M. Detection of honey bee viruses in Argentinian stingless bees (Hymenoptera: Apidae). Insectes Soc. 2018, 65, 191–197. [Google Scholar] [CrossRef]
  66. Dalmon, A.; Gayral, P.; Decante, D.; Klopp, C.; Bigot, D.; Thomasson, M.; AHerniou, E.; Alaux, C.; Conte, Y. Le Viruses in the invasive hornet Vespa velutina. Viruses 2019, 11, 1041. [Google Scholar] [CrossRef] [Green Version]
  67. Payne, A.N.; Shepherd, T.F.; Rangel, J. The detection of honey bee (Apis mellifera)-associated viruses in ants. Sci. Rep. 2020, 10, 2923–2930. [Google Scholar] [CrossRef] [Green Version]
  68. Chen, Y.P.; Pettis, J.S.; Corona, M.; Chen, W.P.; Li, C.J.; Spivak, M.; Visscher, P.K.; DeGrandi-Hoffman, G.; Boncristiani, H.; Zhao, Y. Israeli acute paralysis virus: Epidemiology, pathogenesis and implications for honey bee health. PLoS Pathog 2014, 10, e1004261. [Google Scholar] [CrossRef]
  69. Mao, W.; Schuler, M.A.; Berenbaum, M.R. Honey constituents up-regulate detoxification and immunity genes in the western honey bee Apis mellifera. Proc. Natl. Acad. Sci. USA 2013, 110, 8842–8846. [Google Scholar] [CrossRef] [Green Version]
  70. Cresswell, J.E.; Thompson, H.M. Comment on “a common pesticide decreases foraging success and survival in honey bees”. Science 2012, 337, 1453. [Google Scholar] [CrossRef] [Green Version]
  71. Tesovnik, T.; Cizelj, I.; Zorc, M.; Čitar, M.; Božič, J.; Glavan, G.; Narat, M. Immune related gene expression in worker honey bee (Apis mellifera carnica) pupae exposed to neonicotinoid thiamethoxam and Varroa mites (Varroa destructor). PLoS ONE 2017, 12, e0187079. [Google Scholar] [CrossRef] [PubMed]
  72. Tesovnik, T.; Zorc, M.; Gregorc, A.; Rinehart, T.; Adamczyk, J.; Narat, M. Immune gene expression in developing honey bees (Apis mellifera L.) simultaneously exposed to imidacloprid and Varroa destructor in laboratory conditions. J. Apic. Res. 2019, 58, 730–739. [Google Scholar] [CrossRef]
  73. Brandt, A.; Gorenflo, A.; Siede, R.; Meixner, M.; Büchler, R. The neonicotinoids thiacloprid, imidacloprid, and clothianidin affect the immunocompetence of honey bees (Apis mellifera L.). J. Insect Physiol. 2016, 86, 40–47. [Google Scholar] [CrossRef] [PubMed]
  74. Osterman, J.; Wintermantel, D.; Locke, B.; Jonsson, O.; Semberg, E.; Onorati, P.; Forsgren, E.; Rosenkranz, P.; Rahbek-Pedersen, T.; Bommarco, R. Clothianidin seed-treatment has no detectable negative impact on honeybee colonies and their pathogens. Nat. Commun. 2019, 10, 692–704. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  75. Siviter, H.; Bailes, E.J.; Martin, C.D.; Oliver, T.R.; Koricheva, J.; Leadbeater, E.; Brown, M.J.F. Agrochemicals interact synergistically to increase bee mortality. Nature 2021, 596, 389–392. [Google Scholar] [CrossRef]
  76. Alaux, C.; Kemper, N.; Kretzschmar, A.; Le Conte, Y. Brain, physiological and behavioral modulation induced by immune stimulation in honeybees (Apis mellifera): A potential mediator of social immunity? Brain Behav. Immun. 2012, 26, 1057–1060. [Google Scholar] [CrossRef] [Green Version]
  77. Brodschneider, R.; Crailsheim, K. Nutrition and health in honey bees. Apidologie 2010, 41, 278–294. [Google Scholar] [CrossRef]
  78. Cotter, S.C.; Simpson, S.J.; Raubenheimer, D.; Wilson, K. Macronutrient balance mediates trade-offs between immune function and life history traits. Funct. Ecol. 2011, 25, 186–198. [Google Scholar] [CrossRef]
  79. Frizzera, D.; Del Fabbro, S.; Ortis, G.; Zanni, V.; Bortolomeazzi, R.; Nazzi, F.; Annoscia, D. Possible side effects of sugar supplementary nutrition on honey bee health. Apidologie 2020, 51, 594–608. [Google Scholar] [CrossRef]
  80. Desneux, N.; Bernal, J.S. Genetically modified crops deserve greater ecotoxicological scrutiny. Ecotoxicology 2010, 19, 1642–1644. [Google Scholar] [CrossRef]
  81. O’Callaghan, M.; Glare, T.R.; Burgess, E.P.J.; Malone, L.A. Effects of plants genetically modified for insect resistance on nontarget organisms. Annu. Rev. Entomol. 2005, 50, 271–292. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  82. Shelton, A.M.; Zhao, J.-Z.; Roush, R.T. Economic, ecological, food safety, and social consequences of the deployment of Bt transgenic plants. Annu. Rev. Entomol. 2002, 47, 845–881. [Google Scholar] [CrossRef] [PubMed]
  83. Qaim, M.; Kouser, S. Genetically modified crops and food security. PLoS ONE 2013, 8, e64879. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  84. Duan, J.J.; Marvier, M.; Huesing, J.; Dively, G.; Huang, Z.Y. A meta-analysis of effects of Bt crops on honey bees (Hymenoptera: Apidae). PLoS ONE 2008, 3, e1415. [Google Scholar] [CrossRef]
  85. Devillers, J.; Pham-Delègue, M.-H. Using proteins to assess the poteinal impacts of genentically modifiedplants on honey bees. In Honey Bees: Estimating the Environmental Impact of Chemicals; CRC Press: Boca Raton, FL, USA, 2002; pp. 290–304. ISBN 0203218655. [Google Scholar]
  86. Aldgini, H.M.M.; Al-Abbadi, A.A.; Abu-Nameh, E.S.M.; Alghazeer, R.O. Determination of metals as bio indicators in some selected bee pollen samples from Jordan. Saudi J. Biol. Sci. 2019, 26, 1418–1422. [Google Scholar] [CrossRef]
  87. Nikolić, T.V.; Kojić, D.; Orčić, S.; Batinić, D.; Vukašinović, E.; Blagojević, D.P.; Purać, J. The impact of sublethal concentrations of Cu, Pb and Cd on honey bee redox status, superoxide dismutase and catalase in laboratory conditions. Chemosphere 2016, 164, 98–105. [Google Scholar] [CrossRef]
  88. Polykretis, P.; Delfino, G.; Petrocelli, I.; Cervo, R.; Tanteri, G.; Montori, G.; Perito, B.; Branca, J.J.V.; Morucci, G.; Gulisano, M. Evidence of immunocompetence reduction induced by cadmium exposure in honey bees (Apis mellifera). Environ. Pollut. 2016, 218, 826–834. [Google Scholar] [CrossRef]
  89. Rothman, J.A.; Leger, L.; Kirkwood, J.S.; McFrederick, Q.S. Cadmium and selenate exposure affects the honey bee microbiome and metabolome, and bee-associated bacteria show potential for bioaccumulation. Appl. Environ. Microbiol. 2019, 85, e01411-19. [Google Scholar] [CrossRef] [Green Version]
  90. Sadowska, M.; Gogolewska, H.; Pawelec, N.; Sentkowska, A.; Krasnodębska-Ostręga, B. Comparison of the contents of selected elements and pesticides in honey bees with regard to their habitat. Environ. Sci. Pollut. Res. 2019, 26, 371–380. [Google Scholar] [CrossRef] [Green Version]
  91. Fisogni, A.; Hautekèete, N.; Piquot, Y.; Brun, M.; Vanappelghem, C.; Michez, D.; Massol, F. Urbanization drives an early spring for plants but not for pollinators. Oikos 2020, 129, 1681–1691. [Google Scholar] [CrossRef]
  92. Appler, R.H.; Frank, S.D.; Tarpy, D.R. Within-colony variation in the immunocompetency of managed and feral honey bees (Apis mellifera L.) in different urban landscapes. Insects 2015, 6, 912–925. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  93. Dabour, K.; Al Naggar, Y.; Masry, S.; Naiem, E.; Giesy, J.P. Cellular alterations in midgut cells of honey bee workers (Apis millefera L.) exposed to sublethal concentrations of CdO or PbO nanoparticles or their binary mixture. Sci. Total Environ. 2019, 651, 1356–1367. [Google Scholar] [CrossRef]
  94. AL Naggar, Y.; Dabour, K.; Masry, S.; Sadek, A.; Naiem, E.; Giesy, J.P. Sublethal effects of chronic exposure to CdO or PbO nanoparticles or their binary mixture on the honey bee (Apis millefera L.). Environ. Sci. Pollut. Res. 2020, 27, 19004–19015. [Google Scholar] [CrossRef] [PubMed]
  95. Sharma, V.P.; Kumar, N.R. Changes in honeybee behaviour and biology under the influence of cellphone radiations. Curr. Sci. 2010, 98, 1376–1378. [Google Scholar]
  96. Santhosh Kumar, S. Colony collapse disorder (CCD) in honey bees caused by EMF radiation. Bioinformation 2018, 14, 521–524. [Google Scholar] [CrossRef] [PubMed]
  97. Lupi, D.; Tremolada, P.; Colombo, M.; Giacchini, R.; Benocci, R.; Parenti, P.; Parolini, M.; Zambon, G.; Vighi, M. Effects of pesticides and electromagnetic fields on honeybees: A field study using biomarkers. Int. J. Environ. Res. 2020, 14, 107–122. [Google Scholar] [CrossRef]
  98. Odemer, R.; Odemer, F. Effects of radiofrequency electromagnetic radiation (RF-EMF) on honey bee queen development and mating success. Sci. Total Environ. 2019, 661, 553–562. [Google Scholar] [CrossRef]
  99. Clermont, A.; Eickermann, M.; Kraus, F.; Hoffmann, L.; Beyer, M. Correlations between land covers and honey bee colony losses in a country with industrialized and rural regions. Sci. Total Environ. 2015, 532, 1–13. [Google Scholar] [CrossRef]
  100. O’Neal, S.T.; Anderson, T.D.; Wu-Smart, J.Y. Interactions between pesticides and pathogen susceptibility in honey bees. Curr. Opin. Insect Sci. 2018, 26, 57–62. [Google Scholar] [CrossRef] [Green Version]
  101. Pettis, J.S.; Vanengelsdorp, D.; Johnson, J.; Dively, G. Pesticide exposure in honey bees results in increased levels of the gut pathogen Nosema. Naturwissenschaften 2012, 99, 153–158. [Google Scholar] [CrossRef] [Green Version]
  102. Di, G.; Cavaliere, V.; Annoscia, D.; Varricchio, P.; Caprio, E.; Nazzi, F. Neonicotinoid clothianidin adversely affects insect immunity and promotes replication of a viral pathogen in honey bees. Proc. Natl. Acad. Sci. USA 2013, 110, 18466–18471. [Google Scholar] [CrossRef] [Green Version]
  103. Dussaubat, C.; Maisonnasse, A.; Crauser, D.; Tchamitchian, S.; Bonnet, M.; Cousin, M.; Kretzschmar, A.; Brunet, J.-L.; Le Conte, Y. Combined neonicotinoid pesticide and parasite stress alter honeybee queens’ physiology and survival. Sci. Rep. 2016, 6, 31430–31436. [Google Scholar] [CrossRef]
  104. Aufauvre, J.; Misme-Aucouturier, B.; Viguès, B.; Texier, C.; Delbac, F.; Blot, N. Transcriptome analyses of the honeybee response to Nosema ceranae and insecticides. PLoS ONE 2014, 9, e91686. [Google Scholar] [CrossRef]
  105. Retschnig, G.; Neumann, P.; Williams, G.R. Thiacloprid-Nosema ceranae interactions in honey bees: Host survivorship but not parasite reproduction is dependent on pesticide dose. J. Invertebr. Pathol. 2014, 118, 18–19. [Google Scholar] [CrossRef]
  106. Diao, Q.; Li, B.; Zhao, H.; Wu, Y.; Guo, R.; Dai, P.; Chen, D.; Wang, Q.; Hou, C. Enhancement of chronic bee paralysis virus levels in honeybees acute exposed to imidacloprid: A Chinese case study. Sci. Total Environ. 2018, 630, 487–494. [Google Scholar] [CrossRef]
  107. Tosi, S.; Nieh, J.C.; Sgolastra, F.; Cabbri, R.; Medrzycki, P. Neonicotinoid pesticides and nutritional stress synergistically reduce survival in honey bees. Proc. R. Soc. B Biol. Sci. 2017, 284, 20171711–20171719. [Google Scholar] [CrossRef] [Green Version]
  108. Sánchez-bayo, F.; Goulson, D.; Pennacchio, F.; Nazzi, F.; Goka, K.; Desneux, N. Are bee diseases linked to pesticides ?—A brief review. Environ. Int. 2016, 89–90, 7–11. [Google Scholar] [CrossRef]
  109. Wu-Smart, J.; Spivak, M. Sub-lethal effects of dietary neonicotinoid insecticide exposure on honey bee queen fecundity and colony development. Sci. Rep. 2016, 6, 32108–32119. [Google Scholar] [CrossRef]
  110. Tong, L.; Nieh, J.C.; Tosi, S. Combined nutritional stress and a new systemic pesticide (flupyradifurone, Sivanto®) reduce bee survival, food consumption, flight success, and thermoregulation. Chemosphere 2019, 237, 12408–12416. [Google Scholar] [CrossRef] [Green Version]
  111. Foley, K.; Fazio, G.; Jensen, A.B.; Hughes, W.O.H. Nutritional limitation and resistance to opportunistic Aspergillus parasites in honey bee larvae. J. Invertebr. Pathol. 2012, 111, 68–73. [Google Scholar] [CrossRef]
  112. Koch, H.; Brown, M.J.; Stevenson, P.C. The role of disease in bee foraging ecology. Curr. Opin. Insect Sci. 2017, 21, 60–67. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  113. Dolezal, A.G.; Carrillo-Tripp, J.; Judd, T.M.; Allen Miller, W.; Bonning, B.C.; Toth, A.L. Interacting stressors matter: Diet quality and virus infection in honeybee health. R. Soc. Open Sci. 2019, 6, 181803–181813. [Google Scholar] [CrossRef] [Green Version]
  114. Zhao, Y.; Heerman, M.; Peng, W.; Evans, J.D.; Rose, R.; DeGrandi-Hoffman, G.; Simone-Finstrom, M.; Li, J.; Li, Z.; Cook, S.C. The dynamics of deformed wing virus concentration and host defensive gene expression after Varroa mite parasitism in honey bees, Apis mellifera. Insects 2019, 10, 16. [Google Scholar] [CrossRef] [Green Version]
  115. Straub, L.; Williams, G.R.; Vidondo, B.; Khongphinitbunjong, K.; Retschnig, G.; Schneeberger, A.; Chantawannakul, P.; Dietemann, V.; Neumann, P. Neonicotinoids and ectoparasitic mites synergistically impact honeybees. Sci. Rep. 2019, 9, 8159–8168. [Google Scholar] [CrossRef]
  116. Annoscia, D.; Brown, S.P.; Di Prisco, G.; De Paoli, E.; Del Fabbro, S.; Frizzera, D.; Zanni, V.; Galbraith, D.A.; Caprio, E.; Grozinger, C.M. Haemolymph removal by Varroa mite destabilizes the dynamical interaction between immune effectors and virus in bees, as predicted by Volterra’s model. Proc. R. Soc. B 2019, 286, 20190331–20190339. [Google Scholar] [CrossRef] [Green Version]
  117. van Dooremalen, C.; Stam, E.; Gerritsen, L.; Cornelissen, B.; van der Steen, J.; van Langevelde, F.; Blacquière, T. Interactive effect of reduced pollen availability and Varroa destructor infestation limits growth and protein content of young honey bees. J. Insect Physiol. 2013, 59, 487–493. [Google Scholar] [CrossRef]
  118. Aufauvre, J.; Biron, D.G.; Vidau, C.; Fontbonne, R.; Roudel, M.; Diogon, M.; Viguès, B.; Belzunces, L.P.; Delbac, F.; Blot, N. Parasite-insecticide interactions: A case study of Nosema ceranae and fipronil synergy on honeybee. Sci. Rep. 2012, 2, 326–332. [Google Scholar] [CrossRef]
  119. Zheng, H.-Q.; Gong, H.-R.; Huang, S.-K.; Sohr, A.; Hu, F.-L.; Chen, Y.P. Evidence of the synergistic interaction of honey bee pathogens Nosema ceranae and deformed wing virus. Vet. Microbiol. 2015, 177, 1–6. [Google Scholar] [CrossRef]
  120. Alaux, C.; Brunet, J.; Dussaubat, C.; Mondet, F.; Tchamitchan, S.; Cousin, M.; Brillard, J.; Baldy, A.; Belzunces, L.P.; Le Conte, Y. Interactions between Nosema microspores and a neonicotinoid weaken honeybees (Apis mellifera). Environ. Microbiol. 2010, 12, 774–782. [Google Scholar] [CrossRef] [Green Version]
  121. Tesovnik, T.; Zorc, M.; Ristanić, M.; Glavinić, U.; Stevanović, J.; Narat, M.; Stanimirović, Z. Exposure of honey bee larvae to thiamethoxam and its interaction with Nosema ceranae infection in adult honey bees. Environ. Pollut. 2020, 256, 113443. [Google Scholar] [CrossRef]
  122. Coulon, M.; Schurr, F.; Martel, A.-C.; Cougoule, N.; Bégaud, A.; Mangoni, P.; Di Prisco, G.; Dalmon, A.; Alaux, C.; Ribière-Chabert, M. Influence of chronic exposure to thiamethoxam and chronic bee paralysis virus on winter honey bees. PLoS ONE 2019, 14, e0220703. [Google Scholar] [CrossRef] [Green Version]
  123. Coulon, M.; Schurr, F.; Martel, A.-C.; Cougoule, N.; Bégaud, A.; Mangoni, P.; Dalmon, A.; Alaux, C.; Le Conte, Y.; Thiéry, R. Metabolisation of thiamethoxam (a neonicotinoid pesticide) and interaction with the chronic bee paralysis virus in honeybees. Pestic. Biochem. Physiol. 2018, 144, 10–18. [Google Scholar] [CrossRef]
  124. De Miranda, J.R.; Doublet, V.; Labarussias, M.; De Miranda, J.R.; Moritz, R.F.A.; Paxton, R.J. Bees under stress: Sublethal doses of a neonicotinoid pesticide and pathogens interact to elevate honey bee mortality across the life cycle. Environ. Microbiol. 2015, 17, 969–983. [Google Scholar] [CrossRef]
  125. Odemer, R.; Nilles, L.; Linder, N.; Rosenkranz, P. Sublethal effects of clothianidin and Nosema spp. on the longevity and foraging activity of free flying honey bees. Ecotoxicology 2018, 27, 527–538. [Google Scholar] [CrossRef]
  126. Vidau, C.; Diogon, M.; Aufauvre, J.; Fontbonne, R.; Viguès, B.; Brunet, J.-L.; Texier, C.; Biron, D.G.; Blot, N.; El Alaoui, H. Exposure to sublethal doses of fipronil and thiacloprid highly increases mortality of honeybees previously infected by Nosema ceranae. PLoS ONE 2011, 6, e21550. [Google Scholar] [CrossRef] [Green Version]
  127. Morfin, N.; Goodwin, P.H.; Guzman-Novoa, E. Interaction of varroa destructor and sublethal clothianidin doses during the larval stage on subsequent adult honey bee (Apis mellifera L.) health, cellular immunity, deformed wing virus levels and differential gene expression. Microorganisms 2020, 8, 858. [Google Scholar] [CrossRef]
  128. Reyes-quintana, M.; Espinosa-montaño, L.G.; Prieto-merlos, D.; Koleoglu, G.; Petukhova, T.; Correa-benítez, A.; Guzman-novoa, E. Impact of Varroa destructor and deformed wing virus on emergence, cellular immunity, wing integrity and survivorship of Africanized honey bees in Mexico. J. Invertebr. Pathol. 2019, 164, 43–48. [Google Scholar] [CrossRef]
  129. Blanken, L.J.; van Langevelde, F.; van Dooremalen, C. Interaction between Varroa destructor and imidacloprid reduces flight capacity of honeybees. Proc. R. Soc. B Biol. Sci. 2015, 282, 20151738. [Google Scholar] [CrossRef] [Green Version]
  130. Francis, R.M.; Nielsen, S.L.; Kryger, P. Varroa-virus interaction in collapsing honey bee colonies. PLoS ONE 2013, 8, e57540. [Google Scholar] [CrossRef] [Green Version]
  131. Almasri, H.; Tavares, D.A.; Diogon, M.; Pioz, M.; Alamil, M.; Sené, D.; Tchamitchian, S.; Cousin, M.; Brunet, J.-L.; Belzunces, L.P. Physiological effects of the interaction between Nosema ceranae and sequential and overlapping exposure to glyphosate and difenoconazole in the honey bee Apis mellifera. Ecotoxicol. Environ. Saf. 2021, 217, 112258–112268. [Google Scholar] [CrossRef]
  132. Grassl, J.; Holt, S.; Cremen, N.; Peso, M.; Hahne, D.; Baer, B. Synergistic effects of pathogen and pesticide exposure on honey bee (Apis mellifera) survival and immunity. J. Invertebr. Pathol. 2018, 159, 78–86. [Google Scholar] [CrossRef] [PubMed]
  133. van Dooremalen, C.; Cornelissen, B.; Poleij-Hok-Ahin, C.; Blacquière, T. Single and interactive effects of Varroa destructor, Nosema spp., and imidacloprid on honey bee colonies (Apis mellifera). Ecosphere 2018, 9, e02378. [Google Scholar] [CrossRef] [Green Version]
  134. Porrini, M.P.; Garrido, P.M.; Umpiérrez, M.L.; Porrini, L.P.; Cuniolo, A.; Davyt, B.; González, A.; Eguaras, M.J.; Rossini, C. Effects of synthetic acaricides and Nosema ceranae (microsporidia: Nosematidae) on molecules associated with chemical communication and recognition in honey bee. Vet. Sci. 2020, 7, 199. [Google Scholar] [CrossRef] [PubMed]
  135. Bird, G.; Wilson, A.E.; Williams, G.R.; Hardy, N.B. Parasites and pesticides act antagonistically on honey bee health. J. Appl. Ecol. 2021, 58, 997–1005. [Google Scholar] [CrossRef]
  136. Wintermantel, D.; Locke, B.; Andersson, G.K.S.; Semberg, E.; Forsgren, E.; Osterman, J.; Pedersen, T.R.; Bommarco, R.; Smith, H.G.; Rundlöf, M. Field-level clothianidin exposure affects bumblebees but generally not their pathogens. Nat. Commun. 2018, 9, 5446–5455. [Google Scholar] [CrossRef] [Green Version]
  137. Cutler, G.C.; Scott-Dupree, C.D.; Sultan, M.; McFarlane, A.D.; Brewer, L. A large-scale field study examining effects of exposure to clothianidin seed-treated canola on honey bee colony health, development, and overwintering success. PeerJ 2014, 2, e652. [Google Scholar] [CrossRef]
  138. Rolke, D.; Fuchs, S.; Grünewald, B.; Gao, Z.; Blenau, W. Large-scale monitoring of effects of clothianidin-dressed oilseed rape seeds on pollinating insects in Northern Germany: Effects on honey bees (Apis mellifera). Ecotoxicology 2016, 25, 1648–1665. [Google Scholar] [CrossRef] [Green Version]
  139. Faita, M.R.; Cardozo, M.M.; Amandio, D.T.T.; Orth, A.I.; Nodari, R.O. Glyphosate-based herbicides and Nosema sp. microsporidia reduce honey bee (Apis mellifera L.) survivability under laboratory conditions. J. Apic. Res. 2020, 59, 332–342. [Google Scholar] [CrossRef]
  140. Gregorc, A.; Silva-Zacarin, E.C.M.; Carvalho, S.M.; Kramberger, D.; Teixeira, E.W.; Malaspina, O. Effects of Nosema ceranae and thiametoxam in Apis mellifera: A comparative study in Africanized and Carniolan honey bees. Chemosphere 2016, 147, 328–336. [Google Scholar] [CrossRef] [Green Version]
  141. Coulon, M.; Dalmon, A.; Di Prisco, G.; Prado, A.; Arban, F.; Dubois, E.; Ribière-Chabert, M.; Alaux, C.; Thiéry, R.; Le Conte, Y. Interactions between thiamethoxam and deformed wing virus can drastically impair flight behavior of honey bees. Front. Microbiol. 2020, 11, 766–777. [Google Scholar] [CrossRef]
  142. Morfin, N.; Goodwin, P.H.; Guzman-Novoa, E. Interaction of field realistic doses of clothianidin and Varroa destructor parasitism on adult honey bee (Apis mellifera L.) health and neural gene expression, and antagonistic effects on differentially expressed genes. PLoS ONE 2020, 15, e0229030. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  143. Paris, L.; Peghaire, E.; Mone, A.; Diogon, M.; Debroas, D.; Delbac, F.; El Alaoui, H. Honeybee gut microbiota dysbiosis in pesticide/parasite co-exposures is mainly induced by Nosema ceranae. J. Invertebr. Pathol. 2020, 172, 107348–1073456. [Google Scholar] [CrossRef] [PubMed]
  144. López, J.H.; Krainer, S.; Engert, A.; Schuehly, W.; Riessberger-Gallé, U.; Crailsheim, K. Sublethal pesticide doses negatively affect survival and the cellular responses in American foulbrood-infected honeybee larvae. Sci. Rep. 2017, 7, 40853–40865. [Google Scholar] [CrossRef] [PubMed]
  145. Dance, C.; Botías, C.; Goulson, D. The combined effects of a monotonous diet and exposure to thiamethoxam on the performance of bumblebee micro-colonies. Ecotoxicol. Environ. Saf. 2017, 139, 194–201. [Google Scholar] [CrossRef]
  146. Renzi, M.T.; Rodríguez-Gasol, N.; Medrzycki, P.; Porrini, C.; Martini, A.; Burgio, G.; Maini, S.; Sgolastra, F. Combined effect of pollen quality and thiamethoxam on hypopharyngeal gland development and protein content in Apis mellifera. Apidologie 2016, 47, 779–788. [Google Scholar] [CrossRef] [Green Version]
  147. Sperandio, G.; Simonetto, A.; Carnesecchi, E.; Costa, C.; Hatjina, F.; Tosi, S.; Gilioli, G. Beekeeping and honey bee colony health: A review and conceptualization of beekeeping management practices implemented in Europe. Sci. Total Environ. 2019, 696, 133795–133806. [Google Scholar] [CrossRef]
  148. Zhang, G.; St. Clair, A.L.; Dolezal, A.; Toth, A.L.; O’Neal, M. Honey bee (hymenoptera: Apidea) pollen forage in a highly cultivated agroecosystem: Limited diet diversity and its relationship to virus resistance. J. Econ. Entomol. 2020, 113, 1062–1072. [Google Scholar] [CrossRef]
  149. Jack, C.J.; Uppala, S.S.; Lucas, H.M.; Sagili, R.R. Effects of pollen dilution on infection of Nosema ceranae in honey bees. J. Insect Physiol. 2016, 87, 12–19. [Google Scholar] [CrossRef] [Green Version]
  150. Dolezal, A.G.; Clair, A.L.S.; Zhang, G.; Toth, A.L.; O’Neal, M.E. Native habitat mitigates feast–famine conditions faced by honey bees in an agricultural landscape. Proc. Natl. Acad. Sci. USA 2019, 116, 25147–25155. [Google Scholar] [CrossRef] [Green Version]
  151. Castelli, L.; Branchiccela, B.; Garrido, M.; Invernizzi, C.; Porrini, M.; Romero, H.; Santos, E.; Zunino, P.; Antúnez, K. Impact of nutritional stress on honeybee gut microbiota, immunity, and Nosema ceranae Infection. Microb. Ecol. 2020, 80, 908–919. [Google Scholar] [CrossRef]
  152. de Jong, E.W.; DeGrandi-Hoffman, G.; Chen, Y.; Graham, H.; Ziolkowski, N. Effects of diets containing different concentrations of pollen and pollen substitutes on physiology, Nosema burden, and virus titers in the honey bee (Apis mellifera L.). Apidologie 2019, 50, 845–858. [Google Scholar] [CrossRef]
  153. Ricigliano, V.A.; Dong, C.; Richardson, L.T.; Donnarumma, F.; Williams, S.T.; Solouki, T.; Murray, K.K. Honey bee proteome responses to plant and cyanobacteria (blue-green algae) diets. ACS Food Sci. Technol. 2020, 1, 17–26. [Google Scholar] [CrossRef]
  154. Jehlík, T.; Kodrík, D.; Krištůfek, V.; Koubová, J.; Sábová, M.; Danihlík, J.; Tomčala, A.; Čapková Frydrychová, R. Effects of Chlorella sp. on biological characteristics of the honey bee Apis mellifera. Apidologie 2019, 50, 564–577. [Google Scholar] [CrossRef]
  155. Charistos, L.; Parashos, N.; Hatjina, F. Long term effects of a food supplement HiveAliveTM on honey bee colony strength and Nosema ceranae spore counts. J. Apic. Res. 2015, 54, 420–426. [Google Scholar] [CrossRef]
  156. Alberoni, D.; Baffoni, L.; Gaggìa, F.; Ryan, P.M.; Murphy, K.; Ross, P.R.; Stanton, C.; Di Gioia, D. Impact of beneficial bacteria supplementation on the gut microbiota, colony development and productivity of Apis mellifera L. Benef. Microbes 2018, 9, 269–278. [Google Scholar] [CrossRef]
  157. Mitton, G.A.; Szawarski, N.; Mitton, F.M.; Iglesias, A.; Eguaras, M.J.; Ruffinengo, S.R.; Maggi, M.D. Impacts of dietary supplementation with p-coumaric acid and indole-3-acetic acid on survival and biochemical response of honey bees treated with tau-fluvalinate. Ecotoxicol. Environ. Saf. 2020, 189, 109917–109924. [Google Scholar] [CrossRef]
  158. Szawarski, N.; Saez, A.; Domínguez, E.; Dickson, R.; De Matteis, Á.; Eciolaza, C.; Justel, M.; Aliano, A.; Solar, P.; Bergara, I. Effect of abscisic acid (ABA) combined with two different beekeeping nutritional strategies to confront overwintering: Studies on honey bees’ population dynamics and nosemosis. Insects 2019, 10, 329. [Google Scholar] [CrossRef] [Green Version]
  159. Lamontagne-Drolet, M.; Samson-Robert, O.; Giovenazzo, P.; Fournier, V. The impacts of two protein supplements on commercial honey bee (Apis mellifera L.) colonies. J. Apic. Res. 2019, 58, 800–813. [Google Scholar] [CrossRef]
  160. Cilia, G.; Fratini, F.; Tafi, E.; Turchi, B.; Mancini, S.; Sagona, S.; Nanetti, A.; Cerri, D.; Felicioli, A. Microbial profile of the ventriculum of honey bee (Apis mellifera ligustica spinola, 1806) fed with veterinary drugs, dietary supplements and non-protein amino acids. Vet. Sci. 2020, 7, 76. [Google Scholar] [CrossRef]
  161. Jovanovic, N.M.; Glavinic, U.; Delic, B.; Vejnovic, B.; Aleksic, N.; Mladjan, V.; Stanimirovic, Z. Plant-based supplement containing B-complex vitamins can improve bee health and increase colony performance. Prev. Vet. Med. 2021, 190, 105322. [Google Scholar] [CrossRef]
  162. Glavinic, U.; Stankovic, B.; Draskovic, V.; Stevanovic, J.; Petrovic, T.; Lakic, N.; Stanimirovic, Z. Dietary amino acid and vitamin complex protects honey bee from immunosuppression caused by Nosema ceranae. PLoS ONE 2017, 12, e0187726. [Google Scholar] [CrossRef] [PubMed]
  163. DeGrandi-Hoffman, G.; Chen, Y.; Rivera, R.; Carroll, M.; Chambers, M.; Hidalgo, G.; de Jong, E.W. Honey bee colonies provided with natural forage have lower pathogen loads and higher overwinter survival than those fed protein supplements. Apidologie 2016, 47, 186–196. [Google Scholar] [CrossRef] [Green Version]
  164. Dolasevic, S.; Stevanovic, J.; Aleksic, N.; Glavinic, U.; Deletic, N.; Mladenovic, M.; Stanimirovic, Z. The effect of diet types on some quality characteristics of artificially reared Apis mellifera queens. J. Apic. Res. 2020, 59, 115–123. [Google Scholar] [CrossRef]
  165. Ptaszyńska, A.A.; Borsuk, G.; Zdybicka-Barabas, A.; Cytryńska, M.; Małek, W. Are commercial probiotics and prebiotics effective in the treatment and prevention of honeybee nosemosis C? Parasitol. Res. 2016, 115, 397–406. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  166. Bartlett, L.J. Frontiers in effective control of problem parasites in beekeeping. Int. J. Parasitol. Parasites Wildl. 2022, 17, 263–272. [Google Scholar] [CrossRef] [PubMed]
  167. Toomemaa, K. The synergistic effect of weak oxalic acid and thymol aqueous solutions on Varroa mites and honey bees. J. Apic. Res. 2019, 58, 37–52. [Google Scholar] [CrossRef]
  168. Adamczyk, S.; Lázaro, R.; Pérez-Arquillué, C.; Conchello, P.; Herrera, A. Evaluation of residues of essential oil components in honey after different anti-Varroa treatments. J. Agric. Food Chem. 2005, 53, 10085–10090. [Google Scholar] [CrossRef]
  169. Rosenkranz, P.; Aumeier, P.; Ziegelmann, B. Biology and control of Varroa destructor. J. Invertebr. Pathol. 2010, 103, S96–S119. [Google Scholar] [CrossRef]
  170. Sun, L.; Zhang, X.; Xu, S.; Hou, C.; Xu, J.; Zhao, D.; Chen, Y. Antiviral activities of a medicinal plant extract against sacbrood virus in honeybees. Virol. J. 2021, 18, 83–92. [Google Scholar] [CrossRef]
  171. Tauber, J.P.; Collins, W.R.; Schwarz, R.S.; Chen, Y.; Grubbs, K.; Huang, Q.; Lopez, D.; Peterson, R.; Evans, J.D. Natural product medicines for honey bees: Perspective and protocols. Insects 2019, 10, 356. [Google Scholar] [CrossRef] [Green Version]
  172. Santos, R.C.V.; Lopes, L.Q.S.; dos Alves, C.F.S.; Fausto, V.P.; Pizzutti, K.; Barboza, V.; de Souza, M.E.; Raffin, R.P.; Gomes, P.; Takamatsu, D.; et al. Antimicrobial activity of tea tree oil nanoparticles against American and European foulbrood diseases agents. J. Asia. Pac. Entomol. 2014, 17, 343–347. [Google Scholar] [CrossRef]
  173. Higes, M.; Nozal, M.J.; Alvaro, A.; Barrios, L.; Meana, A.; Martín-Hernández, R.; Bernal, J.L.; Bernal, J. The stability and effectiveness of fumagillin in controlling Nosema ceranae (Microsporidia) infection in honey bees (Apis mellifera) under laboratory and field conditions. Apidologie 2011, 42, 364–377. [Google Scholar] [CrossRef] [Green Version]
  174. Bravo, J.; Carbonell, V.; Sepúlveda, B.; Delporte, C.; Valdovinos, C.E.; Martín-Hernández, R.; Higes, M. Antifungal activity of the essential oil obtained from Cryptocarya alba against infection in honey bees by Nosema ceranae. J. Invertebr. Pathol. 2017, 149, 141–147. [Google Scholar] [CrossRef]
  175. Cilia, G.; Garrido, C.; Bonetto, M.; Tesoriero, D.; Nanetti, A. Effect of api-bioxal® and apiherb® treatments against Nosema ceranae infection in Apis mellifera investigated by two qPCR methods. Vet. Sci. 2020, 7, 125. [Google Scholar] [CrossRef] [PubMed]
  176. Nanetti, A.; Ugolini, L.; Cilia, G.; Pagnotta, E.; Malaguti, L.; Cardaio, I.; Matteo, R.; Lazzeri, L. Seed meals from Brassica nigra and Eruca sativa control artificial Nosema ceranae infections in Apis mellifera. Microorganisms 2021, 9, 949. [Google Scholar] [CrossRef]
  177. Ugolini, L.; Cilia, G.; Pagnotta, E.; Malaguti, L.; Capano, V.; Guerra, I.; Zavatta, L.; Albertazzi, S.; Matteo, R.; Lazzeri, L.; et al. Glucosinolate bioactivation by Apis mellifera workers and its impact on Nosema ceranae infection at the colony level. Biomolecules 2021, 11, 1657. [Google Scholar] [CrossRef]
  178. Hasan, S. A review on nanoparticles: Their synthesis and types. Res. J. Recent Sci 2015, 2277, 2502–2504. [Google Scholar]
  179. Sousa, F.; Ferreira, D.; Reis, S.; Costa, P. Current insights on antifungal therapy: Novel nanotechnology approaches for drug delivery systems and new drugs from natural sources. Pharmaceuticals 2020, 13, 248. [Google Scholar] [CrossRef]
  180. Culha, M.; Kalay, Ş.; Sevim, E.; Pinarbaş, M.; Baş, Y.; Akpinar, R.; Karaoğlu, Ş.A. Biocidal properties of maltose reduced silver nanoparticles against American foulbrood diseases pathogens. Biometals 2017, 30, 893–902. [Google Scholar] [CrossRef]
  181. Li, J.; Heerman, M.C.; Evans, J.D.; Rose, R.; Li, W.; Rodríguez-García, C.; DeGrandi-Hoffman, G.; Zhao, Y.; Huang, S.; Li, Z.; et al. Pollen reverses decreased lifespan, altered nutritional metabolism and suppressed immunity in honey bees (Apis mellifera) treated with antibiotics. J. Exp. Biol. 2019, 222, jeb202077. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  182. Masry, S.H.D.; Taha, T.H.; Botros, W.A.; Mahfouz, H.; Al-Kahtani, S.N.; Ansari, M.J.; Hafez, E.E. Antimicrobial activity of camphor tree silver nano-particles against foulbrood diseases and finding out new strain of Serratia marcescens via DGGE-PCR, as a secondary infection on honeybee larvae. Saudi J. Biol. Sci. 2021, 28, 2067–2075. [Google Scholar] [CrossRef] [PubMed]
  183. Dong, Z.; Wu, Q.; Long, J.; Lu, B.; Zheng, N.; Hu, C.; Chen, P.; Hu, N.; Lu, C.; Pan, M. Silver nanoparticles are effective in controlling microsporidia. Mater. Sci. Eng. C 2021, 125, 112106–112117. [Google Scholar] [CrossRef] [PubMed]
  184. Potts, S.G.; Roberts, S.P.M.; Dean, R.; Marris, G.; Brown, M.A.; Jones, R.; Neumann, P.; Settele, J. Declines of managed honey bees and beekeepers in Europe. J. Apic. Res. 2010, 49, 15–22. [Google Scholar] [CrossRef]
  185. Li, G.; Zhao, H.; Liu, Z.; Wang, H.; Xu, B.; Guo, X. The wisdom of honeybee defenses against environmental stresses. Front. Microbiol. 2018, 9, 722–736. [Google Scholar] [CrossRef]
  186. Tang, J.; Ma, C.; Shi, W.; Chen, X.; Liu, Z.; Wang, H. A National survey of managed honey bee colony winter losses (Apis mellifera) in China (2013–2017). Diversity 2020, 12, 318. [Google Scholar] [CrossRef]
  187. Tawfik, A.I.; Ahmed, Z.H.; Abdel-Rahman, M.F.; Moustafa, A.M. Influence of winter feeding on colony development and the antioxidant system of the honey bee, Apis mellifera. J. Apic. Res. 2020, 59, 752–763. [Google Scholar] [CrossRef]
  188. Abera, A.; Yakob, H.; Yasin, G. Assessment of production system and constraints of bee keeping practices in damot gale woreda, wolaita zone, southern ethiopia. J. Hortic. For. 2016, 6, 109–114. [Google Scholar]
  189. Underwood, R.M.; Traver, B.E.; López-Uribe, M.M. Beekeeping management practices are associated with operation size and beekeepers’ philosophy towards in-hive chemicals. Insects 2019, 10, 10. [Google Scholar] [CrossRef] [Green Version]
Figure 1. The impact on honeybees’ health when exposed to interaction between environmental and ecological stressors.
Figure 1. The impact on honeybees’ health when exposed to interaction between environmental and ecological stressors.
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Figure 2. Factors that can improve honeybees immunity against different stressors.
Figure 2. Factors that can improve honeybees immunity against different stressors.
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El-Seedi, H.R.; Ahmed, H.R.; El-Wahed, A.A.A.; Saeed, A.; Algethami, A.F.; Attia, N.F.; Guo, Z.; Musharraf, S.G.; Khatib, A.; Alsharif, S.M.; et al. Bee Stressors from an Immunological Perspective and Strategies to Improve Bee Health. Vet. Sci. 2022, 9, 199. https://doi.org/10.3390/vetsci9050199

AMA Style

El-Seedi HR, Ahmed HR, El-Wahed AAA, Saeed A, Algethami AF, Attia NF, Guo Z, Musharraf SG, Khatib A, Alsharif SM, et al. Bee Stressors from an Immunological Perspective and Strategies to Improve Bee Health. Veterinary Sciences. 2022; 9(5):199. https://doi.org/10.3390/vetsci9050199

Chicago/Turabian Style

El-Seedi, Hesham R., Hanan R. Ahmed, Aida A. Abd El-Wahed, Aamer Saeed, Ahmed F. Algethami, Nour F. Attia, Zhiming Guo, Syed G. Musharraf, Alfi Khatib, Sultan M. Alsharif, and et al. 2022. "Bee Stressors from an Immunological Perspective and Strategies to Improve Bee Health" Veterinary Sciences 9, no. 5: 199. https://doi.org/10.3390/vetsci9050199

APA Style

El-Seedi, H. R., Ahmed, H. R., El-Wahed, A. A. A., Saeed, A., Algethami, A. F., Attia, N. F., Guo, Z., Musharraf, S. G., Khatib, A., Alsharif, S. M., Naggar, Y. A., Khalifa, S. A. M., & Wang, K. (2022). Bee Stressors from an Immunological Perspective and Strategies to Improve Bee Health. Veterinary Sciences, 9(5), 199. https://doi.org/10.3390/vetsci9050199

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