Regulation of Epidermal Skin Immunity by a Tick Bite

Abstract

Hard ticks are hematophagous arthropods of public health and veterinary importance. Following a tick bite, these arthropods take prolonged, continuous bloodmeals that facilitate pathogen transmission. Successful bloodmeals are attributed to components of the tick saliva that alter inflammation, inhibit hemostasis, and block pain and itch responses in the mammalian skin. Recent studies have reported that extracellular vesicles (EVs) in the saliva enable tick feeding and redirect skin immunity. Notably, the skin epidermis, which interfaces with the external environment, has been mostly neglected when studying the relationship between ticks and their mammalian hosts. Here, we report that Ixodes scapularis EVs enable tick feeding by affecting epidermal γδ T cells frequency and co-receptor expression at the skin site. Epidermal γδ T cells have a critical role in wound healing and interact with keratinocytes, which comprise 95% of the epidermal layer. We further coupled entomological approaches with flow cytometry, single cell RNA sequencing, and animal strains devoid of epidermal γδ T cells to demonstrate that tick EVs disrupt networks involved in keratinocyte proliferation, suggesting an effect on epithelium wound repair. Collectively, this work broadens our knowledge of ectoparasitology, vector-host interactions, and principles of immunology.