Authors

I Mair¹; J Fenn¹; A Wolfenden²; A Lowe²; A Bennett¹; A Muir¹; J Bradley²; KJ Else¹;  ¹ University of Manchester, UK;  ² University of Nottingham, FMHS, Life Sciences, UK

Discussion

Infections caused by species of the gastrointestinal dwelling nematode parasite Trichuris tend to be chronic, and are associated with a significant health burden in humans, livestock and wildlife. A wealth of laboratory work using the model organism Mus musculus (commonly known as the house mouse) experimentally infected with Trichuris muris has established the balance of Type 1 and Type 2 immune responses as the major determinant of disease susceptibility versus worm expulsion. Single parameters such as sex, age, mouse strain, diet, or microbiome composition are known to affect the immune response and susceptibility to disease. However, what shapes the parasite-specific immune response in a multivariate environment? What are the consequences of infection and the strength and/or quality of the concomitant immune response for host health? Taking advantage of the knowledge and tools available for the house mouse, we present a novel study investigating the adaptive immune response to Trichuris in a wild, free-living island population of house mice naturally infected with this endoparasite. Immunological and ecological data were collected from over 200 mice on the Isle of May, UK, sampled across 2018-2019. Trichuris burden across the population showed a typical over-dispersed distribution, and infections were mostly of a chronic nature. The local parasite-specific cytokine response partially overlapped but was significantly different from laboratory mice experimentally infected with either a low or a high dose of Trichuris eggs, especially in response strength. CD4+ T effector/memory phenotypes were linked to cytokine expression but could not explain differences observed between wild and the laboratory setting. Importantly, age and worm burden affected individual Th1/Th2 balance in wild mice in an interrelated fashion. This interdisciplinary study gives first insights into the parasite-specific immune response in a natural system, and through wild-to-lab comparison is able to put the most used laboratory disease model in context. By looking at the immune response to parasites through an ecological lens, taking individual and environmental parameters, and their interactions, into account, we can start to bridge between the laboratory and the wild for more robust translatability of immnunoparasitological research.