The tick vector Ixodes scapularis regulates cross-kingdom interactions through innate immunity

Ticks acquire a bloodmeal from vertebrate hosts, ranging from mammals to reptiles, and are regularly interacting with a variety of microbes via the bloodmeal host or environment. I set out to characterize ways in which ticks interact with a diverse set of organisms, spanning biological kingdoms.One focus of my work was venomous saliva from the tick Ixodes scapularis and its influence on multiple processes that are required for successful blood feeding from a variety of vertebrate hosts. Some of these processes include immune evasion through interference of the host’s defense system and protecting the tick from harmful microbes. I examined the activity of defensins, a family of antimicrobial peptides, found in tick salivary venom. Studies of tick saliva revealed that defensins are secreted into mice and protect ticks against microbes commonly found on the skin of their host. However, several observations point to a role for defensins that is independent of tick–microbe interactions. Through a collaborative effort, I identified a second, intriguing function where these defensins function as mast cell activators through an interaction with a G protein-coupled receptor, MRGPRX2. When ticks feed on mice missing an MRGPRX2 ortholog, they have a decrease in weight, suggesting that activation of this receptor benefits ticks during the feeding process. Another area I explored is the complicated interactions between Ixodes ticks and Borrelia burgdorferi, the causative agent of Lyme disease. In order for ticks transmit B. burgdorferi, the bacteria must migrate from the tick’s midgut to the salivary glands. This migration process is poorly understood. My exploratory research summarized here suggests that this necessary migration of B. burgdorferi is a passive process facilitated by ticks expelling water during blood feeding. Another arm of exploratory research validated previous findings that serum from a common vertebrate host for I. pacificus, the western fence lizard Sceloporus occidentalis, is bactericidal for B. burgdorferi. Both of my exploratory projects are suitable starting points for new research projects which seeks to better characterize cross-kingdom interactions of Ixodes ticks. Together, my studies detailed in this dissertation provide a greater understanding of how ticks survive their varied interaction with a diverse group of organisms