Mouse chymase mast cell protease-4 facilitates blood feeding of <i>Aedes aegypti</i> (Diptera: Culicidae) mosquitoes

Aedes aegypti (Linnaeus) are rapidly spreading across the globe. Evidence suggests that a Type I hypersensitivity reaction, characterized by IgE-mediated mast cell degranulation, may enhance the blood-feeding behavior of Ae. aegypti. Chymases, the mast cell-specific proteases, may play a critical role in this process. To investigate the role of mouse chymase mast cell protease-4 (mMCP-4) on mosquito blood feeding, we incubated bone marrow-derived mast cells with serum from mice sensitized by female Ae. aegypti bites and subsequently challenged the cells with salivary gland proteins (SGPs) from female mosquito. And the degradation of SGPs by mMCP-4 was assessed. Then, the MCP-4 deficient mice were sensitized twice by Ae. aegypti, the first bite on day 0 and the second on day 3. Throughout these experiments, we recorded the total blood meal duration, probing time, and blood feeding of the mosquitoes and analyzed the cutaneous microbiota. We discovered that serum from sensitized mice enhanced mast cell degranulation and chymase release. And mMCP-4 degraded some SGPs, in particular, potentially cleaving the blood-feeding-related salivary protein D7. Mcpt-4 deficiency resulted in prolonged blood-feeding duration during the second exposure, without affecting initial probing behavior. Moreover, Mcpt-4-deficient mice exhibited a reduced proportion of mosquitoes achieving rapid engorgement. Skin microbiome profiling revealed that Mcpt-4 deficiency attenuated the bite-induced expansion of potentially harmful bacterial taxa, including the dominant genus Corynebacterium (Mycobacteriales: Corynebacteriaceae). These findings identify mMCP-4 as a critical mediator of mosquito blood-feeding behavior and a modulator of skin microbial ecology in response to Ae. aegypti bites.