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Open AccessReview

Pathogens Manipulating Tick Behavior—Through a Glass, Darkly

Department of Agriculture, Food and Environment, University of Pisa, via del Borghetto 80, 56124 Pisa, Italy
Pathogens 2020, 9(8), 664; https://doi.org/10.3390/pathogens9080664
Received: 25 June 2020 / Revised: 5 August 2020 / Accepted: 11 August 2020 / Published: 17 August 2020
(This article belongs to the Special Issue Animal Parasitic Diseases)

Abstract

Pathogens can manipulate the phenotypic traits of their hosts and vectors, maximizing their own fitness. Among the phenotypic traits that can be modified, manipulating vector behavior represents one of the most fascinating facets. How pathogens infection affects behavioral traits of key insect vectors has been extensively investigated. Major examples include Plasmodium, Leishmania and Trypanosoma spp. manipulating the behavior of mosquitoes, sand flies and kissing bugs, respectively. However, research on how pathogens can modify tick behavior is patchy. This review focuses on current knowledge about the behavioral changes triggered by Anaplasma, Borrelia, Babesia, Bartonella, Rickettsia and tick-borne encephalitis virus (TBEV) infection in tick vectors, analyzing their potential adaptive significance. As a general trend, being infected by Borrelia and TBEV boosts tick mobility (both questing and walking activity). Borrelia and Anaplasma infection magnifies Ixodes desiccation resistance, triggering physiological changes (Borrelia: higher fat reserves; Anaplasma: synthesis of heat shock proteins). Anaplasma infection also improves cold resistance in infected ticks through synthesis of an antifreeze glycoprotein. Being infected by Anaplasma, Borrelia and Babesia leads to increased tick survival. Borrelia, Babesia and Bartonella infection facilitates blood engorgement. In the last section, current challenges for future studies are outlined.
Keywords: Anaplasma; Babesia; Bartonella; Borrelia; tick ecology and evolution; Lyme disease; host seeking; Ixodes; questing; Rickettsia; tick-borne encephalitis virus; tick management Anaplasma; Babesia; Bartonella; Borrelia; tick ecology and evolution; Lyme disease; host seeking; Ixodes; questing; Rickettsia; tick-borne encephalitis virus; tick management

1. Introduction

Vector-borne diseases (VBDs) are caused by parasites, bacteria and viruses, leading to more than 700,000 deaths yearly [1]. Many VBDs are caused by pathogens vectored by arthropods, among which mosquitoes, sand flies, triatomine bugs and ticks are major players [2,3,4]. Pathogens represent a significant selective pressure on their hosts [5]. The pathogen-host interaction shapes coevolution on both sides. Pathogens can manipulate many phenotypic traits of their hosts, thus maximizing their fitness [6,7,8]. A classic example is represented by Plasmodium infection making host-borne odors more attractive to Anopheles mosquitoes [9,10,11] (but see [12]). Similarly, Leishmania modify the odor of infected hosts, making it more attractive for sand flies [13,14], and Hepatozoon infection can lead to odor changes in snake and frog hosts, which leads to higher feeding rates by Culex pipiens and Culex territans mosquito vectors [15].
Among the phenotypic traits that can be modified, a fascinating category is represented by the behavioral manipulation of vectors to enhance pathogens transmission. According to an earlier classification by Hurd [16], manipulation can be achieved through various mechanisms, such as boosting the chances of contacts among vectors and hosts, reducing vector reproduction to increase nutrients available for the microorganisms, and/or magnifying vector survival.
Behavioral alterations caused by pathogens on their vectors include higher biting rates, reported for Yersinia pestis-infected Xenopsylla cheopis fleas [17], La Crosse virus-infected Aedes triseriatus mosquitoes [18,19], Trypanosoma cruzi-infected Mepraia spinolai kissing bugs [20], and Leishmania mexicana-infected Lutzomyia longipalpis sandflies [21], to cite some key examples. Furthermore, pathogen infection can lead to longer biting duration, as observed for dengue-infected Aedesa egypti [22], Trypanosoma brucei- and Trypanosoma congolense-infected Glossina morsitans morsitans [23,24], Trypanosoma rangeli-infected Rhodnius prolixus [25], and Leishmania major-infected Phlebotomus duboscqi [26]. Increased host searching ability is another possible consequence of the pathogen infection, as recently outlined for young instars of Triatoma pallidipennis and Triatoma longipennis infected by Trypanosoma cruzi, which are more active and able to detect the human odor than non-infected individuals [27]. Moreover, dengue-infected Ae. aegypti mosquitoes show an overall increase of their locomotor ability [28], which can boost their likelihood to detect potential hosts. Lastly, pathogen infection can improve the mating performances of a given arthropod vector, as reported for La Crosse virus-infected Ae. triseriatus; infected mosquitoes mate earlier than non-infected ones [29]. Of note, pathogens-induced behavioral changes in their vectors have been extensively studied by malaria researchers. Higher biting rates and/or longer biting duration have been reported for several Anopheles species infected by Plasmodium spp. [6,30,31,32,33], in some cases coupled with increased survival [34].
Examples of pathogens promoting longer vector lifespan are sparser than behavioral changes, being reported for T. brucei gambiense-infected Glossina palpalis [35] and T. brucei rhodesiense- and T. brucei-infected G. morsitans morsitans [36,37]. In contrast, pathogen infection can also lead to reduced lifespan and fecundity, as reported for Leishmania-infected sandflies [38], Cx. pipiens infected by the Rift Valley fever virus [39], and Trypanosoma-infected triatomine bugs [40,41,42], as examples of possible evolutionary arms races [27].
It has been stressed that manipulation of vector phenotypic traits is more widespread among parasites characterized by a complex life cycle. The latter require a longer and complicated series of events to complete the life cycle, which can be completed more easily through host manipulation [27,43,44]. This scenario may also fit ticks vectoring pathogens responsible of tick-borne diseases. A key example is the complex life cycles of Ixodes ricinus and Ixodes scapularis on multiple hosts over time, which are closely connected with the spread of Lyme borreliosis [45]. However, if compared to the behavioral changes widely investigated in the pathogen-insect vector interactions mentioned above, our knowledge about how pathogens can modify the behavior of tick vectors is patchy, and an overall analysis of the literature available about all major tick-borne pathogens potentially impacting tick behavior is still lacking. In particular, Lyme disease is on the rise [46,47], and a full understanding of how the interaction between its causative agent Borrelia spp. and the tick vectors can lead to behavioral modifications in the latter is of utmost value. The present review focuses on current knowledge on the behavioral changes triggered by Anaplasma, Borrelia, Babesia, Bartonella, Rickettsia and tick-borne encephalitis virus (TBEV) infection in tick vectors, with a focus on their potential adaptive significance and related fitness implications.

2. Pathogens Infecting Ticks Lead to Major Behavioral Changes

Most of the studies about how pathogen infection can affect tick behavior have focused on Borrelia bacteria, the causative agents of Lyme borreliosis, followed by Anaplasma-related studies. Only a few studies have considered the behavioral changes triggered by Babesia, Bartonella, Rickettsia, and TBEV infection. The following subsections review current knowledge about how infection with different pathogens may affect tick behavior. The first subsection is dedicated to the behavioral changes in Borrelia-infected ticks, followed by subsections focusing on the behavioral changes in ticks infected by other pathogens. Since it is hard to disentangle behavioral results from their whole biological context, this review critically discusses behavioral research along with current information on the impact of pathogen infection on other phenotypic traits. Physiological research shedding light on how pathogens can finely manipulate tick basic metabolism shows how this profoundly impacts tick behavior and ecology.

2.1. Behavioral Changes in Borrelia-Infected Ticks

2.1.1. Laboratory Studies

Several studies demonstrate how Borrelia spp. can promote behavioral modifications in tick vectors. A pioneer study by Lefcort and Durden [48] highlighted that nymphs of I. scapularis, infected by Borrelia burgdorferi, showed increased phototaxis and attraction to vertical surfaces compared to non-infected ticks. Both behavioral alterations may be adaptive, boosting Borrelia transmission, since increased phototaxis and attraction to vertical surfaces could increase the likelihood of contact between the tick vector and a potential reservoir host. Additionally, from a physiological point of view, it has been reported that B. burgdorferi-infected I. scapularis ticks can up-regulate the tick histamine release factor (tHRF), allowing a higher blood flow to the bite site and improved vascular permeability. In this way, ticks may engorge more quickly, and the likelihood of becoming infected by Borrelia is also higher [49]. In contrast, B. burgdorferi-infected I. scapularis adults showed lower mobility than uninfected ones, questing at lower heights, being less able to overcome physical obstacles, and avoiding climbing on vertical surfaces [48]. Reduced mobility of adult ticks may represent a by-product of B. burgdorferi infection, possibly non-adaptive for the pathogen or for the tick. However, one may consider that this behavior may be adaptive, since reduced tick movement contribute reducing water and energy loss. Current evidence does not allow any definitive conclusion. While I. scapularis nymphs are crucial for infecting reservoir hosts, thus indirectly newly hatched tick larvae, adults are less prone to feed on reservoir hosts, and so they are not considered mayor players in the spread of Borrelia bacteria [45]. However, these conclusions cannot be generalized for all Ixodes species. Indeed, further research by Romashchenko et al. [50] showed that I. persulcatus adults with a higher prevalence of B. burgdorferi s.l. reached a higher questing height (where the likelihood of intercepting a large host for feeding purposes is higher) than non-infected ticks.
Larvae, nymphs and adults of I. ricinus naturally infected by B. burgdorferi s.l. showed reduced mobility compared to uninfected ones [51]. The same applies to Borrelia-infected adults of the taiga tick, I. persulcatus [51,52,53], suggesting that being infected by B. burgdorferi s.l. boosts mobility of I. persulcatus adults with exoskeleton deformities (i.e., crater-like depressions on the exoskeleton, damaged female scutum and undeveloped palps), collected from a heavy metal polluted area. The reasons at the basis of the observed differences are unclear, and may be partially linked to the short observation time of the mobility experiments (i.e., 3 min). Later, at variance with the results by Alekseev and co-workers, Perret [54] reported that I. ricinus nymphs naturally infected by B. burgdorferi s.l. exposed to desiccating conditions for a prolonged time are more active than uninfected ones. Similarly, Borrelia afzelii-infected I. ricinus nymphs showed higher mobility [i.e., longer walking activity and higher velocity (+10%)] over uninfected ones [55].

2.1.2. Into the Woods—Field Studies

In addition to laboratory research, it is important to consider what is known about the impact of Borrelia infection on ticks in the natural setting. A flagging collection study in the proximity of St. Petersburg (Russia) [56] showed that the appearance of B. burgdorferi s.l.-infected I. persulcatus ticks was related to gradients between the surface and soil temperature and the soil and air relative humidity. More Borrelia-infected nymphs were detected at the temperature interval 10–14 °C compared to 15–20 °C and 21–26 °C (no collected individuals in this latter case) [56]. In dense woodlands nymphs of the western black-legged tick, Ixodes pacificus, infected by B. burgdorferi were found at higher densities on logs and trunks than in the leaf litter [57]. A field study carried out on I. ricinus in western Germany showed that B. burgdorferi s.l.-infected adult females were more frequently present on protective clothes of human volunteers compared to infected females caught by blanket dragging in the same study area [58]. These field results highlight that being infected by Borrelia may contribute to boost host-finding strategies at least for I. pacificus and I. ricinus. Further field data on other Ixodes species are needed. It is also important to determine the effects of other Borrelia genospecies on tick behavioral traits.

2.1.3. Borrelia Manipulation of the Host Odors

Do Borrelia infections manipulate host odor that make hosts more attractive for tick vectors? Similar questions have been addressed about other pathogens, making the host odor more attractive for their insect vectors [13,59]. However, for ticks this question remained unanswered. Recently, van Duijvendijk et al. [60] showed that I. ricinus nymphs were more attracted to bank voles (Myodes glareolus) infected by B. afzelii over uninfected voles, and that infected nymphs feeding on bank voles showed a higher body weight than uninfected ones.
But what happens when the tick vector selects a host not competent for Borrelia transmission? Is the pathogen able to manipulate the tick vector boosting avoidance of the incompetent host? Berret and Voordouw [61] attempted a reply to both questions, showing that being infected by rodent- or bird-specialized Borrelia genospecies did not affect attraction (in terms of questing rates)to mouse odor. Thus, no evidence for the qualitative manipulation hypothesis [6] in the Borrelia-Ixodes interaction has been detected.

2.1.4. Ixodes Behavior Meets Physiology

Borrelia affects tick physiology in several ways. For example, B. burgdorferi infecting I. scapularis salivary glands can usurp a tick salivary protein, salp15, which binds to the spirochetes protecting them from antibody-mediated killing; thus, facilitating infection in mice [62]. The studies summarized above (with few exceptions, see [51,52,53]) highlight that Borrelia infection–as a general trend–impacts tick mobility, with special reference to host-seeking activity. One may consider that a more mobile tick is exposed to a higher risk of desiccation (thus needing to move more often in the ground litter to recover water), and may also need higher energy reserves, because of its increased metabolic activity [63]. The study by Herrmann and Gern [64] shows that the infection by B. burgdorferi s.l. makes I. ricinus ticks more resistant to desiccation when exposed to challenging thermo-hygrometric conditions. The effect was more pronounced on female ticks than on males and nymphs, and highest survival was noted for B. afzelii-infected ticks [64]. A further study examined I. ricinus nymphs collected in the field, showing that Borrelia-infected ones lived longer than uninfected conspecifics when exposed to unfavorable thermo-hygrometric parameters [55].
As concerns the impact of Borrelia infection on tick energy reserves, it has been reported that I. ricinus nymphs questing in the field have a higher fat content when infected by B. burgdorferi s.l. if compared to uninfected ones [65]. The same study clarified that Borrelia exploited only a tiny fraction of these energy reserves, thus the tick can benefit from the increased fat reserves for its own metabolism [65]. As stressed by Herrmann and Gern [63], ticks water recovering occurs through active absorption of external aqueous vapor, and this process is costly from an energetic point of view. Thus, the higher energy reserves of Borrelia-infected ticks can contribute to allow a higher resistance to desiccation.
Borrelia burgdorferi s.l. infection and energy reserves affect horizontal mobility in I. ricinus nymphs. Ticks with high-fat reserves are more prone to explore dryer areas, but—among them—infected individuals stay longer in a fixed position [66]. This partially contrasts with the earlier findings by Lefcort and Durden [48]. Anyway, it has been claimed that Borrelia manipulates I. Ricinus nymphs to remain still, waiting for possible hosts, even under desiccating conditions that usually increase walking activity in non-infected conspecifics [66]. The overall picture is interesting and outlines how Borrelia infection contribute in multiple ways to its own and vector fitness. Remaining still under challenging thermo-hygrometric conditions is highly dangerous for ticks, and only individuals with abundant energy reserves can perform a prolonged recovery of water vapor from the air [67]. The adaptive significance of this behavior deserves further studies, as well as validation of the findings on other Ixodes species.
Lastly, understanding how the behavioral changes characterizing Borrelia-infected ticks may contribute to the spread of Lyme disease is a crucial, but neglected, research topic. A theoretical model developed by Gassner and Hartemink [45] stresses how behavioral changes triggered by Borrelia infection may contribute to an increased transmission risk. Applying a next-generation matrix approach the authors showed that the increased tick vector survival deeply affects the basic reproduction number R0 for Borrelia pathogens.

2.2. Behavioral Changes in Anaplasma-Infected Ticks

Anaplasma infection leads to important physiological changes in Ixodes ticks, impacting tick survival, questing, and feeding activity [68,69,70]. Indeed, as recently highlighted by Cabezas-Cruz et al. [71], Anaplasma phagocytophilum infecting I. scapularis manipulates the expression of key genes, boosting in turn both vector fitness and the pathogen transmission [68,72]. Three major facts related to Anaplasma infection on ticks deserve consideration.
First, ticks exposed to challenging thermo-hygrometric conditions experience a high risk of desiccation. Anaplasma phagocytophilum infecting I. scapularis ticks induce the synthesis of heat shock proteins (i.e., hsp20 and hsp70), which reduce the risk of desiccation, thus enhancing tick survival rates [73]. From a behavioral point of view, gene knock-down of these hsp is linked with reduced questing speed in I. scapularis males, but with relevant changes according to the tested temperature. At 22 °C, only the knock-down of hsp70 gene leads to a significant decrease in tick questing activity (−50%) [73]. Anaplasma phagocytophilum infection does not downregulate the I. scapularis production of the tick protective antigen subolesin, which–if knocked down artificially—leads to reduced questing rates (i.e., −50% and −66% at 4 °C and 37 °C, respectively) [73], among other negative effects on tick biology [71]. The production of another crucial protein for vectors of A. phagocytophilum, such as I. scapularis and I. ricinus, the tudor staphylococcal nuclease, is not affected by the pathogen, thus minimizing damage for tick feeding (assessed in term of tick weight), thus their survival [74].
Second, being exposed to cold temperatures during the winter may lead to significantly higher mortality rates in tick populations. Anaplasma infection can lead to beneficial effects on its tick vectors. Indeed, it has been showed that the infection of I. scapularis nymphs by A. phagocytophilum trigger the synthesis of an antifreeze glycoprotein that protect ticks from cold [75].
Third, A. phagocytophilum infecting the salivary glands of I. scapularis facilitates the infection process through inhibition of the intrinsic apoptosis pathway, while tick cells respond through the extrinsic apoptosis pathway limiting the infection and boosting vector feeding and survival [69,71,76,77].
Overall, the interaction between A. phagocytophilum-I. scapularis is one of the better studied pathogen-tick relationships, with fully clarified mechanisms magnifying tick and pathogen fitness. Applying this successful approach for other important Anaplasma species (e.g., A. marginale, A. centrale, A. ovis and A. platys) and their tick vectors is an important timely challenge.

2.3. Behavioral Changes in Babesia-Infected Ticks

At variance with the plethora of studies on the effect of Borrelia infection on tick behavior, the impact of Babesia infection on tick vectors has been considered only in a couple of studies. First, Randolph [78] showed that Babesia microti infection magnified the feeding success (in terms of mean engorged weight) and survival (in terms of the percentage molt of larvae to nymphs) of the shrew tick Ixodes trianguliceps. Both changes are not linked to the level of infection by B. microti [78]. Later, Hu et al. [79] focused on the potential effect of B. microti infection on I. scapularis feeding time, engorged body weight, and molting rate. Being infected delays the tick engorgement, but the body weight of nymphs engorged on infected hosts is higher than that of the conspecifics that fed on uninfected ones. Larvae, but not nymphs, fed on infected hosts show higher molting rates than those that fed on non-infected hamsters. These differences are not detected testing various tick instars on a different host, i.e., Peromyscus leucopus mice [79]. The mechanisms that promote feeding success, development and survival of Babesia-infected ticks are unknown.

2.4. Behavioral Changes in Bartonella-Infected Ticks

Studies on the behavioral effects of Bartonella infection in ticks are limited. Recently, the salivary glands transcriptome of I. ricinus females infected or not by Bartonella henselae was investigated. Bartonella henselae infection of salivary glands up-regulate I. ricinus serine protease inhibitor (IrSPI), a member of the BPTI/Kunitz family of serine protease inhibitors, and IrSPI silencing strongly reduces weight of I. ricinus feeding adults [80].

2.5. Behavioral Changes in Rickettsia-Infected Ticks

Despite the public health importance of rickettsiosis vectored by ticks, our knowledge about how the Rickettsia infection may affect the behavior of tick vectors is limited. Frątczak et al. [81] showed that I. ricinus adult males and females are attracted toward an area irradiated by a 900 MHz electromagnetic field in a radiation-shielded tube. Ticks infected by Rickettsia spp. as well as those co-infected by Rickettsia spp. and Borrelia s.l. are more attracted by the electromagnetic field compared to the uninfected ones [81]. Understanding the effects of anthropogenic environmental modifications on the pathogen-tick interaction and the related changes in vector behavior represents a highly valuable area of research, which is of practical interest for public health.

2.6. Behavioral Changes in TBEV-Infected Ticks

Ixodid ticks feeding on humans or animals show a higher TBEV prevalence compared to field-collected ticks from the same area. This is clear with I. ricinus from Germany [82] as well I. persulcatus and Ixodes pavlovskyi from Russia [83,84]. Two main hypotheses have been formulated to explain these findings. First, the TBEV infection magnifies tick mobility and host-seeking activity. Second, feeding boosts the titer of TBEV already present in unfed questing ticks to a detectable level. The study by Belova et al. [85] provided data in support of both theories. Ixodes ricinus adults infected by TBEV trying to reach a bait are more active and tolerant than non-infected ones when exposed to growing concentrations of the repellent N,N-diethyl-meta-toluamide (DEET). Of note, about 6% of the infected adults can go over an area where DEET was formulated at 1%, while none of the uninfected ticks could do so [85].
Furthermore, it should be noted that TBEV-infected I. persulcatus females are more active, showing a higher mobility both in terms of walking speed and length of the trajectory when trying to reach a bait [86]. Moreover, I. persulcatus infected with the TBEV reach a higher questing height compared to uninfected conspecifics [50,53].

3. Concluding Remarks and Outstanding Challenges for a Research Agenda

This analysis of current knowledge about how, when and why pathogens trigger behavioral changes in their tick vectors shows that most studies focused on Ixodes species infected by Borrelia bacteria, followed by research on Anaplasma-Ixodes interactions. Only a limited number of studies investigated tick behavioral changes associated to infection by Babesia, Bartonella, Rickettsia, and TBEV.
However, even if limited, the knowledge available on the topic contributes to depict a fascinating scenario. As a general trend, being infected by Borrelia and TBEV substantially increase the overall tick mobility, with special reference to exploiting higher questing heights (this is likely connected with increased phototaxis), often coupled with a higher walking speed and longer walking activity, if compared to non-infected ticks. Noteworthy analogies have been found examining changes triggered post-Borrelia and Anaplasma infection. Both pathogens magnify desiccation resistance of Ixodes ticks (Figure 1). This has been linked to fine physiological changes, i.e., storing higher fat reserves in Borrelia-infected ticks, and synthesizing heat shock proteins in Anaplasma-infected ticks. Anaplasma also improves cold resistance in infected ticks. Additionally, being infected by both pathogens, as well as by B. microti, allowed ticks to achieve a longer survival. Babesia infection also led to higher feeding success (i.e., higher engorged weight), a successful engorgement through upregulation of tHRF and IrSPI characterizes Borrelia- and Bartonella-infected ticks, respectively (Figure 1). Overall, behavioral and physiological changes triggered by pathogens substantially contribute to the tick fitness [63,71], fostering a win-win strategy in the pathogen-tick interaction [69].
Following the criteria expressed for parasite/pathogen-host interactions [7], the term “manipulation” can be used only when the research shows direct fitness benefits (thus an adaptive value of the observed change) for the infecting pathogen, mainly improving its transmission and dispersal rates. This is not disconnected from benefits for the tick vector, often including a longer survival (Figure 1). In other cases, reducing the infection (as in the A. phagocytophilum-Ixodes interaction) or lowering its detrimental effects, can also lead to significant changes, which can be beneficial for the vector. Even the pathological state triggered by the infection can lead to behavioral changes [7,87], which may even reduce the vectorial ability of the involved species. These seem the case of earlier studies showing reduced feeding rates in Cx. pipiens infected by the Rift Valley fever virus [39], as well as the decreased flight activity in Cx. tarsalis infected by the Western equine encephalomyelitis virus [88]. Other pathogen-vector interactions need to be studied further, e.g., the vesicular stomatitis virus-Culicoides sonorensis one, which led to a decrease in the midge biting behavior 2 days’ post-inoculation (DPI), followed by a sharp increase 3 DPI, but not 4 DPI [89]. Besides these examples on insects, a possible case fitting this category can be that of B. burgdorferi-infecting I. scapularis adults, which results in lower tick mobility, with detrimental effects also on questing [48]. Overall, caution remains the first and most useful rule when using the term “adaptive”.
In conclusion, based on the analysis of the literature considered in this review, there are some points that can be useful for developing a perspective research agenda.
Despite the wide diversity of tick species worldwide [90], only Ixodes species have been considered in studies analyzing pathogen-related behavioral changes. How pathogens affect behavioral traits of other tick vectors of huge medical importance, e.g., those belonging to the genera Amblyomma, Dermacentor, and Rhipicephalus, is still overlooked.
Most of the studies have been carried out on Anaplasma- and Borrelia-Ixodes interactions; more research efforts on other key tick-borne pathogens (with special reference to Babesia, Coxiella, Ehrlichia, Rickettsia, and Theileria species) are urgently needed, elucidating the physiological pathways promoting vector manipulation, as recently carried out for Anaplasma and Bartonella research [69,71,80].
Standardizing methods for behavioral research is crucial to allow data comparisons. For example, high reproducibility of questing-related data can be obtained using mechatronic arenas, which also reduce animal testing in laboratory [91], and allows the dissection of host-borne cues [92]. The use of mechatronic arenas also allows repeated testing, thus assessing both intra- and inter-individual variability (e.g., questing success and responses to repellents) of the affected traits in highly standardized conditions over time.
While most studies focused on the effect of pathogen infection on mobility, questing and feeding activities, one may consider, they affect the timing of mating (as showed for Ae. triseriatus infected by La Crosse virus, [29]), mate recognition and mating success of ticks? To the best of my knowledge, this issue has never been investigated.
Moving the focus from studying single traits to a more systematic analysis of all behavioral traits potentially altered by the pathogen infection, and how they correlate each other, represents a major challenge for future research [7].
Both for Borrelia and TBEV-infected ticks, field data have been found extremely useful, fitting the behavioral changes observed in laboratory, which may be partially responsible of enhanced host-seeking activities. Further field research focusing on the impact of other pathogen infections on tick behavioral and ecological traits is needed.
Lastly, the role of manipulation is still not considered in most epidemiological models [10], and the behavioral differences between infected and uninfected vectors need to be carefully evaluated for the correct development and implementation of tick control tools within the Integrated Vector Management and One Heath approaches [2,93,94].

Funding

This study received no external funding.

Acknowledgments

The author is grateful to F. Mancianti for inviting this Review and to J. Beier for his critical revision of the manuscript. R. Ricciardi kindly assisted during manuscript preparation. The author sincerely thanks J. Gathany (CDC-PHIL) for providing the photo of I. pacificus used in Figure 1. Most of the reviewed literature focused on Borrelia- and Anaplasma-triggered behavioral changes in ticks; thus, a photo I. pacificus was selected for Figure 1, being this species a vector of both.

Conflicts of Interest

The author declares no conflict of interest.

References

  1. WHO. Vector Borne Diseases. Available online: https://www.who.int/news-room/fact-sheets/detail/vector-borne-diseases (accessed on 22 June 2020).
  2. Benelli, G.; Duggan, M.F. Management of arthropod vector data–Social and ecological dynamics facing the One Health perspective. Acta Trop. 2018, 182, 80–91. [Google Scholar] [CrossRef]
  3. Rosenberg, R.; Lindsey, N.P.; Fischer, M.; Gregory, C.J.; Hinckley, A.F.; Mead, P.S.; Paz-Bailey, G.; Waterman, S.H.; Drexler, N.A.; Kersh, G.J. Vital signs: Trends in reported vectorborne disease cases—United States and Territories, 2004–2016. Morb. Mortal. Wkly. Rep. 2018, 67, 496. [Google Scholar] [CrossRef] [PubMed]
  4. Wilke, A.B.; Beier, J.C.; Benelli, G. Complexity of the relationship between global warming and urbanization–An obscure future for predicting increases in vector-borne infectious diseases. Curr. Opin. Insect Sci. 2019, 35, 1–9. [Google Scholar] [CrossRef] [PubMed]
  5. Mehlhorn, H. Host manipulations by parasites and viruses. In Parasitology Research Monographs; Springer: Berlin, Germany, 2015; Volume 7, ISBN 3319229362. [Google Scholar]
  6. Lefèvre, T.; Thomas, F. Behind the scene, something else is pulling the strings: Emphasizing parasitic manipulation in vector-borne diseases. Infect. Genet. Evol. 2008, 8, 504–519. [Google Scholar] [CrossRef] [PubMed]
  7. Poulin, R. Parasite manipulation of host behavior: An update and frequently asked questions. In Advances in the Study of Behavior; Academic Press: Cambridge, MA, USA, 2010; Volume 41, pp. 151–186. [Google Scholar]
  8. Poulin, R.; Maure, F. Host manipulation by parasites: A look back before moving forward. Trends Parasitol. 2015, 31, 563–570. [Google Scholar] [CrossRef]
  9. Lacroix, R.; Mukabana, W.R.; Gouagna, L.C.; Koella, J.C. Malaria infection increases attractiveness of humans to mosquitoes. PLoS Biol. 2005, 3, 1590–1593. [Google Scholar] [CrossRef]
  10. Cator, L.J.; Lynch, P.A.; Read, A.F.; Thomas, M.B. Do malaria parasites manipulate mosquitoes? Trends Parasitol. 2012, 28, 466–470. [Google Scholar] [CrossRef]
  11. De Moraes, C.M.; Stanczyk, N.M.; Betz, H.S.; Pulido, H.; Sim, D.G.; Read, A.F.; Mescher, M.C. Malaria-induced changes in host odors enhance mosquito attraction. Proc. Natl. Acad. Sci. USA 2014, 111, 11079–11084. [Google Scholar] [CrossRef]
  12. Cator, L.J.; George, J.; Blanford, S.; Murdock, C.C.; Baker, T.C.; Read, A.F.; Thomas, M.B. “Manipulation” without the parasite: Altered feeding behaviour of mosquitoes is not dependent on infection with malaria parasites. Proc. R. Soc. B Biol. Sci. 2013, 280. [Google Scholar] [CrossRef]
  13. O’shea, B.; Rebollar-Tellez, E.; Ward, R.D.; Hamilton, J.G.C.; El Naiem, D.; Polwart, A. Enhanced sandfly attraction to Leishmania-infected hosts. Trans. R. Soc. Trop. Med. Hyg. 2002, 96, 117–118. [Google Scholar] [CrossRef]
  14. Nevatte, T.M.; Ward, R.D.; Sedda, L.; Hamilton, J.G.C. After infection with Leishmania infantum, Golden Hamsters (Mesocricetus auratus) become more attractive to female sand flies (Lutzomyia longipalpis). Sci. Rep. 2017, 7, 1–9. [Google Scholar] [CrossRef] [PubMed]
  15. Ferguson, L.V.; Kirk Hillier, N.; Smith, T.G. Influence of Hepatozoon parasites on host-seeking and host-choice behaviour of the mosquitoes Culex territans and Culex pipiens. Int. J. Parasitol. Parasites Wildl. 2013, 2, 69–76. [Google Scholar] [CrossRef] [PubMed]
  16. Hurd, H. Manipulation of Medically Important Insect Vectors by Their Parasites. Annu. Rev. Entomol. 2003, 48, 141–161. [Google Scholar] [CrossRef] [PubMed]
  17. Bacot, A.W.; Martin, C.J. LXVII. Observations on the mechanism of the transmission of plague by fleas. J. Hyg. 1914, 13, 423. [Google Scholar] [PubMed]
  18. Grimstad, P.R.; Ross, Q.E.; Craig, G.B., Jr. Aedes triseriatus (Diptera: Culicidae) and La Crosse Virus: II. Modification of mosquito feeding behavior by virus infection. J. Med. Entomol. 1980, 17, 1–7. [Google Scholar] [CrossRef]
  19. Jackson, B.T.; Brewster, C.C.; Paulson, S.L. La Crosse virus infection alters blood feeding behavior in Aedes triseriatus and Aedes albopictus (Diptera: Culicidae). J. Med. Entomol. 2012, 49, 1424–1429. [Google Scholar] [CrossRef]
  20. Botto-Mahan, C.; Cattan, P.E.; Medel, R. Chagas disease parasite induces behavioural changes in the kissing bug Mepraia spinolai. Acta Trop. 2006, 98, 219–223. [Google Scholar] [CrossRef]
  21. Killick-Kendrick, R.; Leaney, A.J.; Ready, P.D.; Molyneux, D.H. Leishmania in phlebotomid sandflies-IV. The transmission of Leishmania mexicana amazonensis to hamsters by the bite of experimentally infected Lutzomyia longipalpis. Proc. R. Soc. London. Ser. B. Biol. Sci. 1977, 196, 105–115. [Google Scholar]
  22. Platt, K.B.; Linthicum, K.J.; Myint, K.S.A.; Innis, B.L.; Lerdthusnee, K.; Vaughn, D.W. Impact of dengue virus infection on feeding behavior of Aedes aegypti. Am. J. Trop. Med. Hyg. 1997, 57, 119–125. [Google Scholar] [CrossRef]
  23. Jenni, L.; Molyneux, D.H.; Livesey, J.L.; Galun, R. Feeding behaviour of tsetse flies infected with salivarian trypanosomes. Nature 1980, 283, 383–385. [Google Scholar] [CrossRef]
  24. Roberts, L.W. Probing by Glossina morsitans morsitans and transmission of Trypanosoma (Nannomonas) congolense. Am. J. Trop. Med. Hyg. 1981, 30, 948–951. [Google Scholar] [CrossRef] [PubMed]
  25. D’alessandro, A.; Mandel, S. Natural infections and behavior of Trypanosoma rangeli and Trypanosoma cruzi in the vector Rhodnius prolixus in Colombia. J. Parasitol. 1969, 55, 846–852. [Google Scholar] [CrossRef]
  26. Beach, R.; Kiilu, G.; Leeuwenburg, J. Modification of sand fly biting behavior by Leishmania leads to increased parasite transmission. Am. J. Trop. Med. Hyg. 1985, 34, 278–282. [Google Scholar] [CrossRef] [PubMed]
  27. Ramírez-González, M.G.; Flores-Villegas, A.L.; Salazar-Schettino, P.M.; Gutiérrez-Cabrera, A.E.; Rojas-Ortega, E.; Córdoba-Aguilar, A. Zombie bugs? Manipulation of kissing bug behavior by the parasite Trypanosoma cruzi. Acta Trop. 2019, 200, 105177. [Google Scholar] [CrossRef] [PubMed]
  28. Lima-Camara, T.N.; Bruno, R.V.; Luz, P.M.; Castro, M.G.; Lourenço-de-Oliveira, R.; Sorgine, M.H.F.; Peixoto, A.A. Dengue infection increases the locomotor activity of Aedes aegypti females. PLoS ONE 2011, 6, e17690. [Google Scholar] [CrossRef]
  29. Reese, S.M.; Beaty, M.K.; Gabitzsch, E.S.; Blair, C.D.; Beaty, B.J. Aedes triseriatus females transovarially infected with La Crosse virus mate more efficiently than uninfected mosquitoes. J. Med. Entomol. 2009, 46, 1152–1158. [Google Scholar] [CrossRef]
  30. Wekesa, J.W.; Copeland, R.S.; Mwangi, R.W. Effect of Plasmodium falciparum on blood feeding behavior of naturally infected Anopheles mosquitoes in western Kenya. Am. J. Trop. Med. Hyg. 1992, 47, 484–488. [Google Scholar] [CrossRef]
  31. Anderson, R.A.; Koella, J.C.; Hurd, H. The effect of Plasmodium yoelii nigeriensis infection on the feeding persistence of Anopheles stephensi Liston throughout the sporogonic cycle. Proc. R. Soc. B Biol. Sci. 1999, 266, 1729–1733. [Google Scholar] [CrossRef]
  32. Koella, J.C.; Packer, M.J. Malaria parasites enhance blood-feeding of their naturally infected vector Anopheles punctulatus. Parasitology 1996, 113, 105–109. [Google Scholar] [CrossRef]
  33. Koella, J.C.; Rieu, L.; Paul, R.E.L. Stage-specific manipulation of a mosquito’s host-seeking behavior by the malaria parasite Plasmodium gallinaceum. Behav. Ecol. 2002, 13, 816–820. [Google Scholar] [CrossRef]
  34. Schwartz, A.; Koella, J.C. Trade-offs, conflicts of interest and manipulation in Plasmodium-mosquito interactions. Trends Parasitol. 2001, 17, 189–194. [Google Scholar] [CrossRef]
  35. Duke, A.L. On the effect on the longevity of G. palpalis of trypanosome infections. Ann. Trop. Med. Parasitol. 1928, 22, 25–32. [Google Scholar] [CrossRef]
  36. Baker, J.R.; Robertson, D.H.H. An experiment on the infectivity to Glossina morsitans of a strain of Trypanosoma rhodesiense and of a strain of T. brucei, with some observations on the longevity of infected flies. Ann. Trop. Med. Parasitol. 1957, 51, 121–135. [Google Scholar]
  37. Maudlin, I.; Welburn, S.C.; Milligan, P.J.M. Trypanosome infections and survival in tsetse. Parasitology 1998, 116, 23–28. [Google Scholar] [CrossRef] [PubMed]
  38. El Sawaf, B.M.; El Sattar, S.A.; Shehata, M.G.; Lane, R.P.; Morsy, T.A. Reduced longevity and fecundity in Leishmania-infected sand flies. Am. J. Trop. Med. Hyg. 1994, 51, 767–770. [Google Scholar] [CrossRef]
  39. Turell, M.J.; Gargan, T.P.; Bailey, C.L. Culex pipiens (Diptera: Culicidae) morbidity and mortality associated with Rift Valley fever virus infection. J. Med. Entomol. 1985, 22, 332–337. [Google Scholar] [CrossRef]
  40. Fellet, M.R.; Lorenzo, M.G.; Elliot, S.L.; Carrasco, D.; Guarneri, A.A. Effects of infection by Trypanosoma cruzi and Trypanosoma rangeli on the reproductive performance of the vector Rhodnius prolixus. PLoS ONE 2014, 9, 26–32. [Google Scholar] [CrossRef]
  41. Peterson, J.K.; Graham, A.L.; Elliott, R.J.; Dobson, A.P.; Chávez, O.T. Trypanosoma cruziTrypanosoma rangeli co-infection ameliorates negative effects of single trypanosome infections in experimentally infected Rhodnius prolixus. Parasitology 2016, 143, 1157–1167. [Google Scholar] [CrossRef]
  42. Cordero-Montoya, G.; Flores-Villegas, A.L.; Salazar-Schettino, P.M.; Vences-Blanco, M.O.; Rocha-Ortega, M.; Gutiérrez-Cabrera, A.E.; Rojas-Ortega, E.; Córdoba-Aguilar, A. The cost of being a killer’s accomplice: Trypanosoma cruzi impairs the fitness of kissing bugs. Parasitol. Res. 2019, 118, 2523–2529. [Google Scholar] [CrossRef]
  43. Cézilly, F.; Thomas, F.; Médoc, V.; Perrot-Minnot, M.J. Host-manipulation by parasites with complex life cycles: Adaptive or not? Trends Parasitol. 2010, 26, 311–317. [Google Scholar] [CrossRef]
  44. Schmid Hempel, P. Evolutionary Parasitologythe Integrated Study of Infections, Immunology, Ecology, and Genetics; OUP Oxford: Oxford, UK, 2011; ISBN 0199229481. [Google Scholar]
  45. Gassner, F.; Hartemink, N. Tick–Borrelia interactions: Burden or benefit? In Ecology of Parasite-Vector Interactions; Wageningen Academic Publishers: Wageningen, The Netherlands, 2013; pp. 141–154. [Google Scholar]
  46. Levi, T.; Kilpatrick, A.M.; Mangel, M.; Wilmers, C.C. Deer, predators, and the emergence of Lyme disease. Proc. Natl. Acad. Sci. USA 2012, 109, 10942–10947. [Google Scholar] [CrossRef] [PubMed]
  47. Benelli, G.; Maggi, F.; Canale, A.; Mehlhorn, H. Lyme disease is on the rise—How about tick repellents? A global view. Entomol. Gen. 2019, 39, 61–72. [Google Scholar] [CrossRef]
  48. Lefcort, H.; Durden, L.A. The effect of infection with Lyme disease spirochetes (Borrelia burgdorferi) on the phototaxis, activity, and questing height of the tick vector Ixodes scapularis. Parasitology 1996, 113, 97–103. [Google Scholar] [CrossRef] [PubMed]
  49. Dai, J.; Narasimhan, S.; Zhang, L.; Liu, L.; Wang, P.; Fikrig, E. Tick histamine release factor is critical for Ixodes scapularis engorgement and transmission of the Lyme disease agent. PLoS Pathog. 2010, 6. [Google Scholar] [CrossRef] [PubMed]
  50. Romashchenko, A.V.; Ratushnyak, A.S.; Zapara, T.A.; Tkachev, S.E.; Moshkin, M.P. The correlation between tick (Ixodes persulcatus Sch.) questing behaviour and synganglion neuronal responses to odours. J. Insect Physiol. 2012, 58, 903–910. [Google Scholar] [CrossRef] [PubMed]
  51. Alekseev, A.N.; Jensen, P.M.; Dubinina, H.V.; Smirnova, L.A.; Makrouchina, N.A.; Zharkov, S.D. Peculiarities of behaviour of taiga (Ixodes persulcatus) and sheep (Ixodes ricinus) ticks (Acarina: Ixodidae) determined by different methods. Folia Parasitol. (Praha). 2000, 47, 147–153. [Google Scholar] [CrossRef]
  52. Alekseev, A.N.; Dubinina, H.V. Symbiotical relationships in the complicated vector-pathogen system. Dokl. Akad. Nauk. 1994, 338, 259–261. [Google Scholar]
  53. Alekseev, A.N. Tick pathogen interactions: Behaviour of infected and uninfected ticks (Ixodidae). In Acarology IX; Mitchell, R., Horn, D.J., Needham, G.R., Welbourn, W.C., Eds.; Ohio Biological Survey: Columbus, OH, USA, 1996; Volume 1, pp. 113–115. [Google Scholar]
  54. Perret, J.L. Computer-assisted Laboratory Observations and Field Studies of the Host-finding Behaviour of the Tick ’Ixodes ricinus’ (Acarina: Ixodidae): Ecological Implications of Climate and Light. Ph.D. Thesis, University of Neuchátel, Neuchátel, Switzerland, 2003. [Google Scholar]
  55. Gassner, F. Tick Tactics: Interactions Between Habitat Characteristics, Hosts and Microorganisms in Relation to the Biology of the Sheep Tick Ixodes Ricinus. Ph.D. Thesis, Wageningen University, Wageningen, The Netherlands, 2010. [Google Scholar]
  56. Alekseev, A.N.; Dubinina, H.V. Abiotic parameters and diel and seasonal activity of Borrelia-infected and uninfected Ixodes persulcatus (Acarina: Ixodidae). J. Med. Entomol. 2000, 37, 9–15. [Google Scholar] [CrossRef]
  57. Lane, R.S.; Mun, J.; Peribáñez, M.A.; Stubbs, H.A. Host-seeking behavior of Ixodes pacificus (Acari: Ixodidae) nymphs in relation to environmental parameters in dense-woodland and woodland-grass habitats. J. Vector Ecol. 2007, 32, 342–357. [Google Scholar] [CrossRef]
  58. Faulde, M.K.; Robbins, R.G. Tick infestation risk and Borrelia burgdorferi s.l. infection-induced increase in host-finding efficacy of female Ixodes ricinus under natural conditions. Exp. Appl. Acarol. 2008, 44, 137. [Google Scholar] [CrossRef]
  59. Robinson, A.; Busula, A.O.; Voets, M.A.; Beshir, K.B.; Caulfield, J.C.; Powers, S.J.; Verhulst, N.O.; Winskill, P.; Muwanguzi, J.; Birkett, M.A.; et al. Plasmodium-associated changes in human odor attract mosquitoes. Proc. Natl. Acad. Sci. USA 2018, 115, E4209–E4218. [Google Scholar] [CrossRef] [PubMed]
  60. Van Duijvendijk, G.; Van Andel, W.; Fonville, M.; Gort, G.; Hovius, J.W.; Sprong, H.; Takken, W. A Borrelia afzelii infection increases larval tick burden on Myodes glareolus (Rodentia: Cricetidae) and Nymphal Body Weight of Ixodes ricinus (Acari: Ixodidae). J. Med. Entomol. 2018, 54, 422–428. [Google Scholar] [CrossRef]
  61. Berret, J.; Voordouw, M.J. Lyme disease bacterium does not affect attraction to rodent odour in the tick vector. Parasites Vectors 2015, 8, 1–9. [Google Scholar] [CrossRef] [PubMed]
  62. Ramamoorthi, N.; Narasimhan, S.; Pal, U.; Bao, F.; Yang, X.F.; Fish, D.; Anguita, J.; Norgard, M.V.; Kantor, F.S.; Anderson, J.F.; et al. The Lyme disease agent exploits a tick protein to infect the mammalian host. Nature 2005, 436, 573–577. [Google Scholar] [CrossRef] [PubMed]
  63. Herrmann, C.; Gern, L. Search for blood or water is influenced by Borrelia burgdorferi in Ixodes ricinus. Parasites Vectors 2015, 8, 4–11. [Google Scholar] [CrossRef]
  64. Herrmann, C.; Gern, L. Survival of Ixodes ricinus (Acari: Ixodidae) under challenging conditions of temperature and humidity is influenced by Borrelia burgdorferi sensu lato infection. J. Med. Entomol. 2010, 47, 1196–1204. [Google Scholar] [CrossRef]
  65. Herrmann, C.; Voordouw, M.J.; Gern, L. Ixodes ricinus ticks infected with the causative agent of Lyme disease, Borrelia burgdorferi sensu lato, have higher energy reserves. Int. J. Parasitol. 2013, 43, 477–483. [Google Scholar] [CrossRef]
  66. Herrmann, C.; Gern, L. Do the level of energy reserves, hydration status and Borrelia infection influence walking by Ixodes ricinus (Acari: Ixodidae) ticks? Parasitology 2012, 139, 330–337. [Google Scholar] [CrossRef]
  67. Randolph, S.E.; Storey, K. Impact of microclimate on immature tick-rodent host interactions (Acari: Ixodidae): Implications for parasite transmission. J. Med. Entomol. 1999, 36, 741–748. [Google Scholar] [CrossRef]
  68. Cabezas-Cruz, A.; Alberdi, P.; Ayllón, N.; Valdés, J.J.; Pierce, R.; Villar, M.; de la Fuente, J. Anaplasma phagocytophilum increases the levels of histone modifying enzymes to inhibit cell apoptosis and facilitate pathogen infection in the tick vector Ixodes scapularis. Epigenetics 2016, 11, 303–319. [Google Scholar] [CrossRef]
  69. de la Fuente, J.; Villar, M.; Cabezas-Cruz, A.; Estrada-Peña, A.; Ayllón, N.; Alberdi, P. Tick–Host–Pathogen Interactions: Conflict and Cooperation. PLoS Pathog. 2016, 12, 1–7. [Google Scholar] [CrossRef] [PubMed]
  70. de la Fuente, J.; Antunes, S.; Bonnet, S.; Cabezas-Cruz, A.; Domingos, A.G.; Estrada-Peña, A.; Johnson, N.; Kocan, K.M.; Mansfield, K.L.; Nijhof, A.M.; et al. Tick-Pathogen Interactions and Vector Competence: Identification of Molecular Drivers for Tick-Borne Diseases. Front. Cell. Infect. Microbiol. 2017, 7, 1–13. [Google Scholar] [CrossRef]
  71. Cabezas-Cruz, A.; Estrada-Peña, A.; Rego, R.O.M.; De la Fuente, J. Tick-pathogen Ensembles: Do molecular interactions lead ecological innovation? Front. Cell. Infect. Microbiol. 2017, 7, 1–5. [Google Scholar] [CrossRef] [PubMed]
  72. Cabezas-Cruz, A.; Alberdi, P.; Valdés, J.J.; Villar, M.; de la Fuente, J. Anaplasma phagocytophilum infection subverts carbohydrate metabolic pathways in the tick vector, Ixodes scapularis. Front. Cell. Infect. Microbiol. 2017, 7, 1–17. [Google Scholar] [CrossRef] [PubMed]
  73. Busby, A.T.; Ayllón, N.; Kocan, K.M.; Blouin, E.F.; de La Fuente, G.; Galindo, R.C.; Villar, M.; de la Fuente, J. Expression of heat shock proteins and subolesin affects stress responses, Anaplasma phagocytophilum infection and questing behaviour in the tick, Ixodes scapularis. Med. Vet. Entomol. 2012, 26, 92–102. [Google Scholar] [CrossRef] [PubMed]
  74. Ayllón, N.; Naranjo, V.; Hajduek, O.; Villar, M.; Galindo, R.C.; Kocan, K.M.; Alberdi, P.; Šíma, R.; Cabezas-Cruz, A.; Rückert, C.; et al. Nuclease Tudor-SN is involved in tick dsRNAMediated RNA interference and feeding but not in defense against flaviviral or Anaplasma phagocytophilum rickettsial infection. PLoS ONE 2015, 10, 1–18. [Google Scholar] [CrossRef]
  75. Neelakanta, G.; Sultana, H.; Fish, D.; Anderson, J.F.; Fikrig, E. Anaplasma phagocytophilum induces Ixodes scapularis ticks to express an antifreeze glycoprotein gene that enhances their survival in the cold. J. Clin. Investig. 2010, 120, 3179–3190. [Google Scholar] [CrossRef]
  76. Ayllón, N.; Villar, M.; Galindo, R.C.; Kocan, K.M.; Šíma, R.; López, J.A.; Vázquez, J.; Alberdi, P.; Cabezas-Cruz, A.; Kopáček, P.; et al. Systems Biology of Tissue-Specific Response to Anaplasma phagocytophilum Reveals Differentiated Apoptosis in the Tick Vector Ixodes scapularis. PLoS Genet. 2015, 11, 1–29. [Google Scholar] [CrossRef]
  77. Villar, M.; Ayllón, N.; Alberdi, P.; Moreno, A.; Moreno, M.; Tobes, R.; Mateos-Hernández, L.; Weisheit, S.; Bell-Sakyi, L.; de la Fuente, J. Integrated metabolomics, transcriptomics and proteomics identifies metabolic pathways affected by Anaplasma phagocytophilum infection in tick cells. Mol. Cell. Proteomics 2015, 14, 3154–3172. [Google Scholar] [CrossRef]
  78. Randolph, S.E. The effect of Babesia microti on feeding and survival in its tick vector, Ixodes trianguliceps. Parasitology 1991, 102, 9–16. [Google Scholar] [CrossRef]
  79. Hu, R.; Hyland, K.E.; Markowski, D. Effects of Babesia microti Infection on Feeding Pattern, Engorged Body Weight, and Molting Rate of Immature Ixodes scapularis (Acari: Ixodidae). J. Med. Entomol. 1997, 34, 559–564. [Google Scholar] [CrossRef]
  80. Liu, X.Y.; de la Fuente, J.; Cote, M.; Galindo, R.C.; Moutailler, S.; Vayssier-Taussat, M.; Bonnet, S.I. IrSPI, a tick serine protease inhibitor involved in tick feeding and Bartonella henselae infection. PLoS Negl Trop Dis 2014, 8, e2993. [Google Scholar] [CrossRef] [PubMed]
  81. Frątczak, M.; Vargová, B.; Tryjanowski, P.; Majláth, I.; Jerzak, L.; Kurimský, J.; Cimbala, R.; Jankowiak, Ł.; Conka, Z.; Majláthová, V. Infected Ixodes ricinus ticks are attracted by electromagnetic radiation of 900 MH. Ticks Tick. Borne. Dis. 2020, 11, 101416. [Google Scholar] [CrossRef] [PubMed]
  82. Süss, J.; Schrader, C.; Falk, U.; Wohanka, N. Tick-borne encephalitis (TBE) in Germany—Epidemiological data, development of risk areas and virus prevalence in field-collected ticks and in ticks removed from humans. Int. J. Med. Microbiol. Suppl. 2004, 293, 69–79. [Google Scholar] [CrossRef]
  83. Mel’nikova, O.V.; Botvinkin, A.D.; Danchinova, G.A. Comparative data on the tick-borne encephalitis virus infectiousness of hungry and satiated taiga ticks (based on the results of an immunoenzyme analysis). Med. Parazitol. (Mosk). 1997, 1, 44–49. [Google Scholar]
  84. Romanenko, V.N.; Kondrat’eva, L.M. The infection of ixodid ticks collected from humans with the tick-borne encephalitis virus in Tomsk city and its suburbs. Parazitologiia 2011, 45, 3–10. [Google Scholar]
  85. Belova, O.A.; Burenkova, L.A.; Karganova, G.G. Different tick-borne encephalitis virus (TBEV) prevalences in unfed versus partially engorged ixodid ticks - Evidence of virus replication and changes in tick behavior. Ticks Tick. Borne Dis. 2012, 3, 240–246. [Google Scholar] [CrossRef]
  86. Alekseev, A.N.; Burenkova, L.A.; Chunikhin, S.P. Behavioral characteristics of Ixodes persulcatus P. Sch. ticks infected with the tick-borne encephalitis virus. Med. Parazitol. (Mosk). 1988, 2, 71–75. [Google Scholar]
  87. Poulin, R. Evolution of parasite life history traits: Myths and reality. Parasitol. Today 1995, 11, 342–345. [Google Scholar] [CrossRef]
  88. Lee, J.H.; Rowley, W.A.; Platt, K.B. Longevity and spontaneous flight activity of Culex tarsalis (Diptera: Culicidae) infected with western equine encephalomyelitis virus. J. Med. Entomol. 2000, 37, 187–193. [Google Scholar] [CrossRef]
  89. Bennett, K.E.; Hopper, J.E.; Stuart, M.A.; West, M.; Drolet, B.S. Blood-feeding behavior of vesicular stomatitis virus infected Culicoides sonorensis (Diptera: Ceratopogonidae). J. Med. Entomol. 2008, 45, 921–926. [Google Scholar] [CrossRef]
  90. Guglielmone, A.A.; Robbins, R.G.; Apanaskevich, D.A.; Petney, T.N.; Estrada-Peña, A.; Horak, I.G. Individual Species Accounts. In The Hard Ticks of the World; Springer: Dordrecht, The Netherlands, 2014; pp. 13–218. [Google Scholar]
  91. Romano, D.; Stefanini, C.; Canale, A.; Benelli, G. Artificial blood feeders for mosquito and ticks—Where from, where to? Acta Trop. 2018, 183, 43–56. [Google Scholar] [CrossRef] [PubMed]
  92. Benelli, G.; Romano, D.; Rocchigiani, G.; Caselli, A.; Mancianti, F.; Canale, A.; Stefanini, C. Behavioral asymmetries in ticks–lateralized questing of Ixodes ricinus to a mechatronic apparatus delivering host-borne cues. Acta Trop. 2018, 178, 176–181. [Google Scholar] [CrossRef] [PubMed]
  93. Dantas-Torres, F.; Chomel, B.B.; Otranto, D. Ticks and tick-borne diseases: A One Health perspective. Trends Parasitol. 2012, 28, 437–446. [Google Scholar] [CrossRef]
  94. Benelli, G.; Senthil-Nathan, S. Together in the Fight against Arthropod-Borne Diseases: A One Health Perspective. Int. J. Environ. Res. Publ. Health. 2018, 16, 4876. [Google Scholar] [CrossRef]
Figure 1. Main behavioral changes caused by pathogen infection of the tick vector. Colored dots indicate different pathogens; pathogen-triggered key physiological changes contributing to increase tick feeding, survival or the vector, and likelihood of coming in contacts with potential hosts are also outlined; TBEV: tick-borne encephalitis virus; tHRF: tick histamine release factor; IrSPI: I. ricinus serine protease inhibitor.
Figure 1. Main behavioral changes caused by pathogen infection of the tick vector. Colored dots indicate different pathogens; pathogen-triggered key physiological changes contributing to increase tick feeding, survival or the vector, and likelihood of coming in contacts with potential hosts are also outlined; TBEV: tick-borne encephalitis virus; tHRF: tick histamine release factor; IrSPI: I. ricinus serine protease inhibitor.
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