Changing the Recipe: Pathogen Directed Changes in Tick Saliva Components

Abstract

Ticks are obligate hematophagous parasites and are important vectors of a wide variety of pathogens. These pathogens include spirochetes in the genus Borrelia that cause Lyme disease, rickettsial pathogens, and tick-borne encephalitis virus, among others. Due to their prolonged feeding period of up to two weeks, hard ticks must counteract vertebrate host defense reactions in order to survive and reproduce. To overcome host defense mechanisms, ticks have evolved a large number of pharmacologically active molecules that are secreted in their saliva, which inhibits or modulates host immune defenses and wound healing responses upon injection into the bite site. These bioactive molecules in tick saliva can create a privileged environment in the host’s skin that tick-borne pathogens take advantage of. In fact, evidence is accumulating that tick-transmitted pathogens manipulate tick saliva composition to enhance their own survival, transmission, and evasion of host defenses. We review what is known about specific and functionally characterized tick saliva molecules in the context of tick infection with the genus Borrelia, the intracellular pathogen Anaplasma phagocytophilum, and tick-borne encephalitis virus. Additionally, we review studies analyzing sialome-level responses to pathogen challenge.

Tick Intrastadial Feeding and Its Role on IgE Production in the Murine Model of Alpha-gal Syndrome: The Tick “Transmission” Hypothesis

“…Dynamic control of the salivary components in tick feeding has been known. The factors that have been known to affect differential salivary gene expression and contents are the host species, host immune status, tick feeding stage over a week of feeding, and the presence of host pathogens (32)(33)(34)(35)(36). Interestingly, high levels of the aGal epitope in males fed on bovine blood were not observed in the case of male ticks fed on mice (see Supplementary Figure S4), which suggests that the enriched aGal epitope in the male salivary gland is host specific.…”

Ticks: More Than Just a Pathogen Delivery Service

“…Recently, many salivary molecules were discovered to be secreted within extracellular vesicles ( Nawaz et al, 2020a ; Nawaz et al, 2020b ; Zhou et al, 2020 ; Oliva Chávez et al, 2021 ), which impact host immune responses, wound healing and feeding success of the tick ( Karim et al, 2002 ; Karim et al, 2005 ; Alarcon-Chaidez et al, 2009 ; Villarreal et al, 2013 ; Shaw et al, 2016 ; Zhou et al, 2020 ; Oliva Chávez et al, 2021 ; Pham et al, 2021 ). Interestingly, salivary extracellular vesicles can modulate the outcome of vector-borne infections, as is the case for A. phagocytophilum and Francisella tularensis ( Oliva Chávez et al, 2021 ).…”

Host Immune Responses to Salivary Components - A Critical Facet of Tick-Host Interactions

“…Ixodid ticks are particularly different from Argasidae in the duration of their attachment to the host; they feed for several days depending on the life stage, as compared to soft ticks, which repeatedly feed for short periods of time ranging from minutes to hours ( Oliver, 1989 ; Sonenshine, 1991 ). Due to the prolonged feeding, hard ticks have developed myriad strategies; they create a feeding cavity by piercing the host skin through the chelicerae that induce a blood pool in the dermis, where ticks inoculate saliva to facilitate blood-feeding, and remain attached to the host ( Francischetti et al., 2009 ; Šimo et al., 2017 ; Boulanger and Wikel, 2021 ; Pham et al., 2021 ; Tirloni et al., 2021 ; Ali et al., 2022 ). These pharmacologically active molecules maintain the blood-feeding cavity and suppress the host defense mechanisms at the bite site ( Nuttall and Labuda, 2004 ; Francischetti et al., 2009 ; Ali et al., 2015a ; Martins et al., 2020 ).…”