Search Results (26)

Aquaculture of molluscs and crustaceans represents an important and expanding sector within global food production. The intensification of these systems has been accompanied by an increased prevalence and severity of infectious diseases, which continue to constrain productivity and sustainability. Current disease management approaches include biosecurity measures, husbandry practices, therapeutics, and selective breeding, which have shown limited efficacy against many emerging pathogens affecting invertebrate species. Unlike finfish, aquatic invertebrates lack adaptive immunity and rely exclusively on innate immune mechanisms, limiting the effectiveness of traditional vaccine strategies. There is growing interest in immunostimulants that enhance innate defenses and support immune priming or trans-generational immune priming (TGIP). This review summarises the current understanding of immune defence mechanisms in molluscs and crustaceans and examines recent progress in the development of immunomodulators and prophylactic interventions aimed at improving health outcomes and disease resilience in invertebrate aquaculture. Full article

Stress is a predisposing factor for pulmonary diseases; however, its effects on the lungs of healthy individuals have not been fully elucidated. Since bovine lactoferrin (bLf) is a powerful immunomodulator, this study aimed to evaluate whether lactoferrin can modulate the effects of chronic stress on humoral and cellular immunity in the lungs. We performed chronic restraint stress (RS) and oral administration of bLf in a BALB/c model, assessing serum corticosterone, body weight, and various lung immunity parameters, including immunoglobulin concentrations in serum and tracheobronchial lavages (TBLs), secretory IgA (S-IgA) levels in TBLs, IgA-secreting plasma cells, relative expression of pIgR, CD4⁺ lymphocyte Th1 and Th2 populations, and antigen-presenting cell (APC) populations in the lungs. Our results demonstrate that stress increases corticosterone and production of total IgA and IgG, while decreasing levels of IgM and S-IgA, promotes a Th1/Th2 profile imbalance, and decreases APC populations. Interestingly, bLf modulates serum corticosterone levels and stress-induced weight loss, and it also modulates humoral and cellular effects produced by chronic stress. These results demonstrate that bLf should be considered a new therapeutic target for further studies, focusing on prophylactic and co-therapeutic administration to treat and prevent respiratory diseases. Full article

Background/Objectives: Chronic obstructive pulmonary disease (COPD) is a global health problem and the third leading contributor to mortality worldwide. This systematic review aims to summarize the results of previous studies tackling the question of the efficacy of long-term prophylaxis of antibiotics in COPD patients, with particular regard to exacerbation rate, time to first exacerbation, health status, airway bacterial load, inflammatory markers, cell counts in sputum samples, and potential adverse events. Results: Four studies found significant improvement in the exacerbation rate in patients receiving antibiotic intervention. One study found doxycycline to have negative effects on patients’ exacerbation outcomes. Two studies recorded a reduction in total airway bacterial load using quantitative culture of sputum samples, but the prevalence of antibiotic-resistant bacteria increased in all studies that measured it. No change in inflammatory markers was observed; however, there was a decline in neutrophil cell counts and, subsequently, reductions in neutrophil elastase concentrations. Methods: PubMed and Web of Science databases were searched for English-language studies presenting data on the prophylactic use of antibiotics in COPD management. All included studies are randomized controlled trials (RCTs) and meet the inclusion criteria. Conclusions: Based on current evidence from RCTs, the prophylactic antibiotic approach utilizing macrolides is the most effective in reducing the incidence of COPD exacerbation. However, the emergence of antibiotic-resistant pathogens is notable. Whether the beneficial effects of macrolides on exacerbation are due to their antibacterial or immunomodulant properties is still inconclusive. Future studies are needed to better understand the interactions between antibiotics and the airway microbiome during COPD exacerbation. Full article

The underdevelopment of adjuvant discovery and diversity, compared to core vaccine technology, is evident. On the other hand, antibiotic resistance is on the list of the top ten threats to global health. Immunomodulatory peptides that target a pathogen and modulate the immune system simultaneously are promising for the development of preventive and therapeutic molecules. Since investigating innate immunity in insects has led to prominent achievements in human immunology, such as toll-like receptor (TLR) discovery, we used the capacity of the immunomodulatory peptides of arthropods with concomitant antimicrobial or antitumor activity. An SVM-based machine learning classifier identified short immunomodulatory sequences encrypted in 643 antimicrobial peptides from 55 foe-to-friend arthropods. The critical features involved in efficacy and safety were calculated. Finally, 76 safe immunomodulators were identified. Then, molecular docking and simulation studies defined the target of the most optimal peptide ligands among all human cell-surface TLRs. SPalf2-453 from a crab is a cell-penetrating immunoadjuvant with antiviral properties. The peptide interacts with the TLR1/2 heterodimer. SBsib-711 from a blackfly is a TLR4/MD2 ligand used as a cancer vaccine immunoadjuvant. In addition, SBsib-711 binds CD47 and PD-L1 on tumor cells, which is applicable in cancer immunotherapy as a checkpoint inhibitor. MRh4-679 from a shrimp is a broad-spectrum or universal immunoadjuvant with a putative Th1/Th2-balanced response. We also implemented a pathway enrichment analysis to define fingerprints or immunological signatures for further in vitro and in vivo immunogenicity and reactogenicity measurements. Conclusively, combinatorial machine learning, molecular docking, and simulation studies, as well as systems biology, open a new opportunity for the discovery and development of multifunctional prophylactic and therapeutic lead peptides. Full article

β-glucan is part of the cell wall of fungi and yeasts and has been known for decades to have immunomodulating effects on boosting immunity against various infections as a pathogen-associated molecular pattern that is able to modify biological responses. β-glucan has been used in rat models and in vitro studies involving sepsis and SIRS with good results, but this supplement has not been evaluated in the treatment of endotoxemia in horses. This study aims to evaluate the effects of preventive supplementation with β-glucan in horses submitted to endotoxemia by means of inflammatory response modulation. Eight healthy horses, both male and female, aged 18 ± 3 months, weighing 300 ± 100 kg of mixed breed, were randomly assigned to two groups of four animals, both of which were subjected to the induction of endotoxemia via the intravenous administration of E. coli lipopolysaccharides (0.1 µg/kg). For 30 days before the induction of endotoxemia, horses in the β-glucan group (GB) received 10 mg/kg/day of β-glucan orally, and horses in the control group (GC) received 10 mg/kg/day of 0.9% sodium chloride orally. The horses were submitted to physical exams, including a hematological, serum biochemistry, and peritoneal fluid evaluation, and the serum quantification of cytokines TNF-α, IL-6, IL-8, and IL-10. For statistical analysis, the normality of residues and homogeneity of variances were verified; then, the variables were analyzed as repeated measures over time, checking the effect of treatment, time, and the interaction between time and treatment. Finally, the averages were compared using Tukey’s test at a significance level of 5%. Horses from both experimental groups presented clinical signs and hematological changes in endotoxemia, including an increase in heart rate and body temperature, neutrophilic leukopenia, an increase in serum bilirubin, glucose, lactate, and an increase in TNF-α, IL-6, and IL-10. Hepatic and renal function were not compromised by β-glucan supplementation. GB presented higher mean values of the serum total protein, globulins, and IL-8 compared to that observed in GC. In the peritoneal fluid, horses from GB presented a lower mean concentration of neutrophils and a higher mean concentration of macrophages compared to the GC. It was concluded that preventive supplementation of β-glucan for thirty days modulated the immune response, as evidenced by increasing serum total proteins, globulins, IL-8, and changes in the type of peritoneal inflammatory cells, without effectively attenuating clinical signs of endotoxemia in horses. Considering the safety of β-glucan in this study, the results suggest the potential clinical implication of β-glucan for prophylactic use in horse endotoxemia. Full article

Rice bran arabinoxylan compound (RBAC) is derived from defatted rice bran enzymatically treated with Lentinus edodes mycelium. This review explores biologically active compounds and mechanisms of action that support RBAC as an immunomodulating nutraceutical in generally healthy and/or aging individuals. Thirty-seven (n = 37) primary research articles fulfilled the selection criteria for review. Most research is based on Biobran MGN-3, which consists of complex heteropolysaccharides with arabinoxylan as its primary structure while also containing galactan and glucan. RBAC was found to invoke immunological activities through direct absorption via the digestive tract and interaction with immune cells at the Peyer’s patches. RBAC was shown to promote innate defence by upregulating macrophage phagocytosis and enhancing natural killer cell activity while lowering oxidative stress. Through induction of dendritic cell maturation, RBAC also augments adaptive immunity by promoting T and B lymphocyte proliferation. RBAC acts as an immunomodulator by inhibiting mast cell degranulation during allergic reactions, attenuating inflammation, and downregulating angiogenesis by modulating cytokines and growth factors. RBAC has been shown to be a safe and effective nutraceutical for improving immune health, notably in aging individuals with reduced immune function. Human clinical trials with geriatric participants have demonstrated RBAC to have prophylactic benefits against viral infection and may improve their quality of life. Further research should explore RBAC’s bioavailability, pharmacodynamics, and pharmacokinetics of the complex heteropolysaccharides within. Translational research to assess RBAC as a nutraceutical for the aging population is still required, particularly in human studies with larger sample sizes and cohort studies with long follow-up periods. Full article

Halophytes and xerophytes, plants with adequate tolerance to high salinity with strong ability to survive in drought ecosystem, have been recognized for their nutritional and medicinal values owing to their comparatively higher productions of secondary metabolites, primarily the phenolics, and the flavonoids, as compared to the normal vegetation in other climatic regions. Given the consistent increases in desertification around the world, which are associated with increasing salinity, high temperature, and water scarcity, the survival of halophytes due to their secondary metabolic contents has prioritized these plant species, which have now become increasingly important for environmental protection, land reclamation, and food and animal-feed security, with their primary utility in traditional societies as sources of drugs. On the medicinal herbs front, because the fight against cancer is still ongoing, there is an urgent need for development of more efficient, safe, and novel chemotherapeutic agents, than those currently available. The current review describes these plants and their secondary-metabolite-based chemical products as promising candidates for developing newer cancer therapeutics. It further discusses the prophylactic roles of these plants, and their constituents in prevention and management of cancers, through an exploration of their phytochemical and pharmacological properties, with a view on immunomodulation. The important roles of various phenolics and structurally diverse flavonoids as major constituents of the halophytes in suppressing oxidative stress, immunomodulation, and anti-cancer effects are the subject matter of this review and these aspects are outlined in details. Full article

Extracellular Vesicles (EVs) are nano-sized double-lipid-membrane-bound structures, acting mainly as signalling mediators between distant cells and, in particular, modulating the immune response and inflammation of targeted cells. Milk and colostrum contain high amounts of EVs that could be exploited as alternative natural systems in antimicrobial fighting. The aim of this study is to evaluate cow colostrum-derived EVs (colosEVs) for their antimicrobial, anti-inflammatory and immunomodulating effects in vitro to assess their suitability as natural antimicrobial agents as a strategy to cope with the drug resistance problem. ColosEVs were evaluated on a model of neonatal calf diarrhoea caused by Escherichia coli infection, a livestock disease where antibiotic therapy often has poor results. Colostrum from Piedmontese cows was collected within 24 h of calving and colosEVs were immediately isolated. IPEC-J2 cell line was pre-treated with colosEVs for 48 h and then infected with EPEC/NTEC field strains for 2 h. Bacterial adherence and IPEC-J2 gene expression analysis (RT-qPCR) of CXCL8, DEFB1, DEFB4A, TLR4, TLR5, NFKB1, MYD88, CGAS, RIGI and STING were evaluated. The colosEVs pre-treatment significantly reduced the ability of EPEC/NTEC strains to adhere to cell surfaces (p = 0.006), suggesting a role of ColosEVs in modulating host–pathogen interactions. Moreover, our results showed a significant decrease in TLR5 (p < 0.05), CGAS (p < 0.05) and STING (p < 0.01) gene expression in cells that were pre-treated with ColosEVs and then infected, thus highlighting a potential antimicrobial activity of ColosEVs. This is the first preliminarily study investigating ColosEV immunomodulatory and anti-inflammatory effects on an in vitro model of neonatal calf diarrhoea, showing its potential as a therapeutic and prophylactic tool. Full article

The COVID-19 pandemic has evolved to immune escape and threatened small children and the elderly with a higher severity and fatality of non-pulmonary diseases. These life-threatening non-pulmonary COVID-19 diseases such as acute necrotizing encephalopathies (ANE) and multisystem inflammatory syndrome in children (MIS-C) are more prevalent in children. However, the mortality of multisystem inflammatory syndrome in adults (MIS-A) is much higher than that of MIS-C although the incidence of MIS-A is lower. Clarification of immunopathogenesis and genetic susceptibility of inflammatory non-pulmonary COVID-19 diseases would provide an appropriate guide for the crisis management and prevention of morbidity and fatality in the ongoing pandemic. This review article described three inflammatory non-pulmonary COVID-19 diseases including (1) meningoencephalitis (ME), (2) acute necrotizing encephalopathies (ANE), and (3) post-infectious multisystem inflammatory syndrome in children (MIS-C) and in adults (MIS-A). To prevent these life-threatening non-pulmonary COVID-19 diseases, hosts carrying susceptible genetic variants should receive prophylactic vaccines, avoid febrile respiratory tract infection, and institute immunomodulators and mitochondrial cocktails as early as possible. Full article

Polyphenols and flavonoids from non-fermented green tea and fully-fermented black tea exhibit antioxidant abilities that function as natural health foods for daily consumption. Nonetheless, evidence regarding prophylactic effects of purple shoot tea on immunomodulation remains scarce. We compared the immunomodulatory effects of different tea processes on oxidative stress and cytokine expressions in lipopolysaccharide (LPS)-stimulated macrophages. Major constituents of four tea products, Taiwan Tea Experiment Station No.12 (TTES No. 12) black and green tea and purple shoot black and purple shoot green tea (TB, TG, PB and PG, respectively), were analyzed to explore the prophylactic effects on expressions of free radicals, nitric oxide (NO), monocyte chemoattractant protein-1 (MCP-1), interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) in LPS-activated RAW264.7 cell models. PG contained abundant levels of total polyphenols, flavonoids, condensed tannins and proanthocyanidins (371.28 ± 3.83; 86.37 ± 1.46; 234.67 ± 10.1; and 24.81 ± 0.75 mg/g, respectively) contributing to excellent free radical scavenging potency. In both the LPS-activated inflammation model and the prophylactic model, all tea extracts suppressed NO secretion in a dose-dependent manner, especially for PG. Intriguingly, most tea extracts enhanced expressions of IL-6 in LPS-stimulated macrophages, except PG. However, all teas disrupted downstream transduction of chemoattractant MCP-1 for immune cell trafficking. In the prophylactic model, all teas inhibited inflammatory responses by attenuating expressions of IL-6 and TNF-α in a dose-dependent manner, especially for TG and PG. Our prophylactic model demonstrated PG exerts robust effects on modulating LPS-induced cytokine expressions of MCP-1, IL-6 and TNF-α through scavenging free radicals and NO. In light of the prophylactic effects on LPS-related inflammation, PG effectively scavenges free radicals to modulate cytokine cascades that could serve as a functional beverage for immunomodulation. Full article

Chronic infection by high-risk human papillomaviruses (HPV) and chronic inflammation are factors associated with the onset and progression of several neoplasias, including cervical cancer. Oncogenic proteins E5, E6, and E7 from HPV are the main drivers of cervical carcinogenesis. In the present article, we review the general mechanisms of HPV-driven cervical carcinogenesis, as well as the involvement of cyclooxygenase-2 (COX-2)/prostaglandin E₂ (PGE₂) and downstream effectors in this pathology. We also review the evidence on the crosstalk between chronic HPV infection and PGE₂ signaling, leading to immune response weakening and cervical cancer development. Finally, the last section updates the current therapeutic and preventive options targeting PGE₂-derived inflammation and HPV infection in cervical cancer. These treatments include nonsteroidal anti-inflammatory drugs, prophylactic and therapeutical vaccines, immunomodulators, antivirals, and nanotechnology. Inflammatory signaling pathways are closely related to the carcinogenic nature of the virus, highlighting inflammation as a co-factor for HPV-dependent carcinogenesis. Therefore, blocking inflammatory signaling pathways, modulating immune response against HPV, and targeting the virus represent excellent options for anti-tumoral therapies in cervical cancer. Full article

Human lymphatic filariae have evolved numerous immune evasion strategies to secure their long-term survival in a host. These strategies include regulation of pattern recognition receptors, mimicry with host glycans and immune molecules, manipulation of innate and adaptive immune cells, induction of apoptosis in effector immune cells, and neutralization of free radicals. This creates an anti-inflammatory and immunoregulatory milieu in the host: a modified Th2 immune response. Therefore, targeting filarial immunomodulators and manipulating the filariae-driven immune system against the filariae can be a potential therapeutic and prophylactic strategy. Filariae-derived immunosuppression can also be exploited to treat other inflammatory diseases and immunopathologic states of parasitic diseases, such as cerebral malaria, and to prevent leishmaniasis. This paper reviews immunomodulatory mechanisms acquired by these filariae for their own survival and their potential application in the development of novel therapeutic approaches against parasitic and inflammatory diseases. Insight into the intricate network of host immune-parasite interactions would aid in the development of effective immune-therapeutic options for both infectious and immune-pathological diseases. Full article

Viruses have evolved diverse strategies to evade the antiviral response of interferons (IFNs). Exogenous IFNs were applied to eliminate the counteracting effect and possess antiviral properties. Caprine parainfluenza virus 3 (CPIV3) and bovine parainfluenza virus type 3 (BPIV3) are important pathogens associated with respiratory diseases in goat and cattle, respectively. To explore the feasibility of type I IFNs for control of CPIV3 and BPIV3 infection, the activated effects of IFN-stimulated genes (ISGs) and the immunomodulation responses of goat IFN-α were detected by transcriptomic analysis. Then, the antiviral efficacy of goat IFN-α and IFN-τ against CPIV3 and BPIV3 infection in MDBK cells was evaluated using different treatment routes at different infection times. The results showed that CPIV3 infection inhibited the production of type I IFNs, whereas exogenous goat IFN-α induced various ISGs, the IFN-τ encoding gene, and a negligible inflammatory response. Consequently, goat IFN-α prophylaxis but not treatment was found to effectively modulate CPIV3 and BPIV3 infection; the protective effect lasted for 1 week, and the antiviral activity was maintained at a concentration of 0.1 μg/mL. Furthermore, the antiviral activity of goat IFN-τ in response to CPIV3 and BPIV3 infection is comparable to that of goat IFN-α. These results corroborate that goat IFN-α and IFN-τ exhibit prophylactic activities in response to ruminant respiratory viral infection in vitro, and should be further investigated for a potential use in vivo. Full article

Multiple Sclerosis (MS) is a serious autoimmune disease. The patient in an advanced state of the disease has restrained mobility and remains handicapped. It is therefore understandable that there is a great need for novel drugs and vaccines for the treatment of MS. Herein we summarise two major approaches applied for the treatment of the disease using peptide molecules alone or conjugated with mannan. The first approach focuses on selective myelin epitope peptide or peptide mimetic therapy alone or conjugated with mannan, and the second on immune-therapy by preventing or controlling disease through the release of appropriate cytokines. In both approaches the use of cyclic peptides offers the advantage of increased stability from proteolytic enzymes. In these approaches, the synthesis of myelin epitope peptides conjugated to mannan is of particular interest as this was found to protect mice against experimental autoimmune encephalomyelitis, an animal model of MS, in prophylactic and therapeutic protocols. Protection was peptide-specific and associated with reduced antigen-specific T cell proliferation. The aim of the studies of these peptide epitope analogs is to understand their molecular basis of interactions with human autoimmune T-cell receptor and a MS-associated human leucocyte antigen (HLA)-DR2b. This knowledge will lead the rational design to new beneficial non-peptide mimetic analogs for the treatment of MS. Some issues of the use of nanotechnology will also be addressed as a future trend to tackle the disease. We highlight novel immunomodulation and vaccine-based research against MS based on myelin epitope peptides and strategies developed in our laboratories. Full article

Kidney transplantation (KT) is the gold standard treatment of end-stage renal disease. Despite progressive advances in organ preservation, surgical technique, intensive care, and immunosuppression, long-term allograft survival has not significantly improved. Among the many peri-operative complications that can jeopardize transplant outcomes, ischemia–reperfusion injury (IRI) deserves special consideration as it is associated with delayed graft function, acute rejection, and premature transplant loss. Over the years, several strategies have been proposed to mitigate the impact of IRI and favor tolerance, with rather disappointing results. There is mounting evidence that adipose stem/stromal cells (ASCs) possess specific characteristics that could help prevent, reduce, or reverse IRI. Immunomodulating and tolerogenic properties have also been suggested, thus leading to the development of ASC-based prophylactic and therapeutic strategies in pre-clinical and clinical models of renal IRI and allograft rejection. ASCs are copious, easy to harvest, and readily expandable in culture. Furthermore, ASCs can secrete extracellular vesicles (EV) which may act as powerful mediators of tissue repair and tolerance. In the present review, we discuss the current knowledge on the mechanisms of action and therapeutic opportunities offered by ASCs and ASC-derived EVs in the KT setting. Most relevant pre-clinical and clinical studies as well as actual limitations and future perspective are highlighted. Full article