First-in-human evaluation of cutaneous innate and adaptive immunomodulation by mosquito bites

Mosquito-borne viruses are a growing global threat. Initial viral inoculation occurs in the skin via the mosquito ‘bite’, eliciting immune responses that shape the establishment of infection and pathogenesis. To understand these phenomena, we assessed the cutaneous innate and adaptive immune responses via controlled Aedes aegypti feedings in humans living in an Aedes -endemic country. Gene expression profiling and immunophenotyping revealed induction of neutrophil degranulation and recruitment of skin-resident dendritic cells and M2-macrophages. As the immune reaction progressed over time, T cell priming and regulatory pathways were upregulated along with a shift to a Th2-driven response and CD8+ T cell activation. In accordance, participants’ bitten skin cells produced less pro-inflammatory cytokines when stimulated by Ae. aegypti salivary gland extract. These results identify key immune genes, cell types, and pathways in the human response to mosquito bites that can be leveraged to develop novel therapeutics and vector-targeted vaccine candidates to arboviral diseases. ![Figure][1] Graphical Abstract ### Competing Interest Statement The authors have declared no competing interest. [1]: pending:yes