Trends in Immunology
Feature ReviewTick host immunity: vector immunomodulation and acquired tick resistance
Section snippets
Evolution of sophisticated hematophagy in ticks and the perplexing immunobiology of tick–host associations
Ticks comprise a diverse group of highly adapted and obligate blood-feeding ectoparasites classified into the Ixodidae (hard tick, see Glossary) and Argasidae (soft tick) families, encompassing 692 and 186 species, respectively [1]. A third ancestral family, the Nuttalliellidae, is represented by a single surviving species that exists only in South Africa [2]. Although there is uncertainty about the precise location or timeline of the origin of ticks, it is likely that they evolved and
Tick immunomodulation of natural hosts
Because ticks (particularly hard tick species) engorge for a prolonged time on permissive vertebrates, including natural or reservoir hosts, they must counteract or circumvent the complex defense mechanisms of the host that have evolved to prevent blood loss and infection. We focus here on the cytological events at the tick bite site and the multidimensional roles of tick saliva proteins, especially their influences on major host defenses, which allow the vectors to successfully secure a blood
Saliva-assisted pathogen transmission
With the exception of a defined set of transovarially transmitted pathogens, most tick-borne diseases are passively transmitted to the host dermis via tick saliva [26,74]. Ticks such as I. scapularis produce multiple SG proteins with anti-hemostatic, anti-inflammatory, and (as shown in many experimental studies) immunosuppressive properties, which can support the transmission of tick-borne pathogens (Table 1) [15,29]. For example, as highlighted in Table 1, transmission of B. burgdorferi,
Acquired tick resistance
Although some tick species such as I. scapularis can feed repeatedly without apparent resistance on their natural or reservoir hosts, for example the white-footed mouse (P. leucopus), some non-natural or incidental hosts can quickly develop strong resistance against tick bites [25]. William Trager first reported this spectacular immunological event in 1939 when guinea pigs were shown to develop robust resistance against multiple infestations by the American dog tick, D. variabilis [17]. This
Contrasting and overlapping immune responses: the possible outcomes of tick–host associations
We discuss here the major hypothesis that the immune responses of natural reservoir hosts versus non-natural incidental hosts might dictate the differing outcomes of tick feeding events. We also present a comparison of these types of host responses.
Concluding remarks: gaps, challenges, and future directions
Ticks, which originated before the first dinosaurs, have evolved a remarkable hematophagy over millions of years of parasitism. Given the monophyletic nature of tick evolution and the unique hematophagy of hard ticks, their vector–host associations are likely to be fundamentally different from those of other blood-feeding arthropods [143,144]. Recent studies involving repeated engorgements of Ixodes tick on mice and guinea pigs have unearthed new paradigms for the concepts of tick immune
Acknowledgments
The authors are thankful to Kathryn Nassar for assistance with the preparation of this manuscript. This study was supported by the National Institute of Allergy and Infectious Diseases, award numbers R01AI080615, AI116620, and P01AI138949 to U.P.
Declaration of interests
The authors declare no conflicts of interest.
Glossary
- Acquired tick resistance (ATR)
- an immunological mechanism that allows specific hosts to develop immunity against repeated infestations by ticks. It develops after multiple successive tick infestations in a non-natural host, leading to tick detachment or death.
- Apyrase
- an ATP-diphosphohydrolase that catalyzes the sequential hydrolysis of ATP to ADP and ADP to AMP, releasing inorganic phosphate. In ticks, apyrase can impair platelet aggregation by breaking down ADP released by activated platelets
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