Tick host immunity: vector immunomodulation and acquired tick resistance

Abstract

Ticks have an unparalleled ability to parasitize diverse land vertebrates. Their natural persistence and vector competence are supported by the evolution of sophisticated hematophagy and remarkable host immune-evasion activities. We analyze the immunomodulatory roles of tick saliva which facilitates their acquisition of a blood meal from natural hosts and allows pathogen transmission. We also discuss the contrasting immunological events of tick-host associations in non-reservoir or incidental hosts, in which the development of acquired tick resistance can deter tick attachment. A critical appraisal of the intricate immunobiology of tick-host associations can plant new seeds of innovative research and contribute to the development of novel preventive strategies against ticks and tick-transmitted infections.

Figure 1:. Schematic representation of the geological time-scale, highlighting major life events, the origin of ticks, and evolution of hematophagy.

Ticks originated and diversified over a wide geological time period in the early Mesozoic era, with a major dispersal in the Tertiary period [1,3,4]. The rapid divergence of major tick families coincided with the divergence of modern birds and placental mammals in the late Cretaceous period (120 – 92 MYA*)[6], suggesting that the latter event might be a driving force in the evolution of distinct hematophagy processes in ticks. *MYA: million years ago.

Figure 2:. Schematic structure of mammalian skin, highlighting major cellular infiltrates at the bite site of a natural host.

Tick (e.g. Ixodes scapularis) engorgement in reservoir [23] or non-resistant [24] hosts results in the infiltration of host immune cells on or around the tick bite site. The variable cellular infiltrates are mostly a mixed population of inflammatory cells, such as neutrophils, lymphocytes, eosinophils, and basophils, with the occasional presence of tissue macrophages (histocytes). Depicted are mild to moderate ulcerations at the tick bite site, along with central invagination and vascular injury, including vascular dilation and extravasation of erythrocytes. This figure was created using  BioRender (https://biorender.com/).

Figure 3:. Tick immunomodulation of major mammalian host responses by tick saliva components.

The tick salivary gland contains a large panel of bioactive molecules that are secreted into the host dermis, targeting host cells and molecules, thereby modulating various host responses that ultimately favor the successful acquisition of a blood meal. Representative examples of identified tick saliva molecules and their effects on selected host responses are shown [26,28,29,170]. For details, please refer to the text and Table 1. This figure was created using  BioRender (https://biorender.com/).

Figure 4:. Acquired tick resistance in a mammalian incidental host.

The image shows the major histological changes at the tick bite sites of an incidental host, such as in guinea pigs, during the genesis of acquired tick resistance via repeated tick bites. The left panel shows the histological parameters at the first tick bite, characterized by the relatively decreased infiltration of immune cells relative to immune, tick-exposed incidental hosts (right panel), which is (depending on the species) mostly comprised of leukocytes and localized granulomas, as well as dermatitis with substantial hemorrhage at the tick bite site [23,24]. As shown in the right panel, during repeated tick exposure, the same host reflects acquired resistance to tick infestation, resulting in the detachment of the vector as an unfed or partially-fed tick. The tick bite site can show histolytic lesions with epidermal hyperplasia and hyperkeratosis, in addition to more intense leukocytic infiltrations with the predominant presence of eosinophils, basophils, and mast cells [23,24]. This figure was created using  BioRender (https://biorender.com/).