Acquired tick resistance in alters infection.

Ticks are obligate hematophagous parasites and pathogen vectors responsible for morbidity and mortality worldwide. is a vector for at least seven pathogens relevant to human and animal health, including the Lyme disease microbe, , and the causative agent of anaplasmosis, . Tick-host interactions affect the maintenance of tick-borne pathogens in a population. Here, we report that repeated larval infestations on the wild host species lead to immune-mediated rejection of the tick, a phenomenon termed acquired tick resistance (ATR). On previously infested mice, we observed that larval feeding success was reduced by over 50%, and fed larvae had decreased blood meal weights compared to larvae fed on naïve hosts. Over sequential infestations, mice exhibited increasingly severe inflammation at tick bite sites characterized by an influx of basophils, eosinophils, neutrophils, and T lymphocytes. Larvae fed on sensitized mice ingested higher quantities of host leukocytes when compared to ticks fed on naïve hosts, which rarely ingested nucleated cells. When challenged with or , larvae fed on sensitized mice ingested more bacteria. Altogether, we demonstrate that reservoir host species develop ATR against larval , which reduces tick feeding success and affects pathogen ingestion by larvae. These results indicate that ATR could impact population dynamics, prevalence of infected ticks, and pathogen circulation in the wild.