# Acquired tick resistance in Peromyscus leucopus alters Ixodes scapularis infection

## TL;DR

Mice that develop resistance to ticks reduce tick feeding success and pathogen spread.

## Contribution

The discovery of acquired tick resistance in Peromyscus leucopus and its impact on tick-borne pathogen transmission.

## Key findings

- Repeated tick infestations in mice lead to immune-mediated rejection of ticks.
- Ticks feeding on resistant mice ingest more host immune cells and pathogens.
- Acquired resistance could reduce tick populations and pathogen circulation.

## Abstract

Ticks are obligate hematophagous parasites and pathogen vectors responsible for morbidity and mortality worldwide. Ixodes scapularis is a vector for at least seven pathogens relevant to human and animal health, including the Lyme disease microbe, Borrelia burgdorferi, and the causative agent of anaplasmosis, Anaplasma phagocytophilum. Tick-host interactions affect the maintenance of tick-borne pathogens in a population. Here, we report that repeated I. scapularis larval infestations on the wild host species Peromyscus leucopus 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 B. burgdorferi or A. phagocytophilum, larvae fed on sensitized mice ingested more bacteria. Altogether, we demonstrate that reservoir host species develop ATR against larval I. scapularis, which reduces tick feeding success and affects pathogen ingestion by larvae. These results indicate that ATR could impact Ixodes population dynamics, prevalence of infected ticks, and pathogen circulation in the wild.