Authors

I Mair²; R Bancroft¹; R Fletcher¹; L Logunova¹; AB Pedersen²; K Else¹;  ¹ University of Manchester, Lydia Becker Institute of Immunology and Inflammation, UK;  ² University of Edinburgh, Institute for Ecology and Evolution, UK

Discussion

The gastrointestinal dwelling nematode parasite Trichuris (whipworm) causes chronic infections, associated with a significant health burden in humans, livestock and wildlife. Understanding host-parasite interactions and adaptations in wild animal systems is important for our understanding of both the host immune response and in assessing the zoonotic potential of such pathogens. Mechanistic insight in to the host immune response to whipworm infections, using laboratory mice experimentally infected with the mouse species of whipworm Trichuris muris , has established the balance of Type 1 and Type 2 immune responses as the major determinant of susceptibility versus resistance to infection. However, in the lab, single parameters, such as diet, sex, genetics, microbiome composition and age are all known to impact the outcome of infection. How these contribute to the quality of the parasite-specific immune response in a natural, multivariate environment, and how this affects host health, is unknown.

To bridge between laboratory findings and a real-world context, we are studying the adaptive immune response to Trichuris muris in a wild, free-living island population of house mice naturally infected with whipworm. Using immunological and ecological data collected from 200 mice on the Isle of May, UK, sampled across 2018-2019 we have previously shown that wild mice harbouring chronic, low-level infections produced lower levels of cytokines in response to Trichuris antigen than laboratory-housed C57BL/6 mice and that the local Trichuris -specific Th1/Th2 balance is positively associated with worm burden in older wild mice.

Building on these data sets, we are currently experimentally testing whether diet supplementation directly, or indirectly, impacts helminth infection through changes in the immune response and/or in the gut microbiota. To harness the potential of diet supplementation as a possible solution to reduce infection burdens and their associated pathology, it is crucial that we disentangle these complex diet-immune response-gut microbiota interactions. Thus, we are combining dietary and immunological interventional experiments in wild mouse populations to determine what drives diet-mediated improvements in helminth resistance and reductions in host harm. I will describe some of our preliminary parasitological and immunological results following our first field trip for this project.