Interactions between the Environment and Genetics determines immune variation in rewilded mice

• Published in: The Journal of immunology (1950) 2022-05, Vol.208 (1_Supplement), p.115-115.23
• Main Authors: Oyesola, Oyebola Oluwakemi, Downie, Alexander E., Barre, Ramya Smithaveni, Chen, Ying-Han, Kiwanuka, Kasalina N, Zaldana, Kimberly, Howard, Nina, Lee, Soo Ching, Devlin, Joseph, Mondragon, Octavio Paloma, Herrmann, Christin, Zhao, Mingming, Koralov, Sergie B., Cadwell, Kenneth, Graham, Andrea L, Loke, P'ng
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.208.Supp.115.23

Immune responses to pathogens and vaccination can be varied with some individuals inducing optimal responses while others do not. The host genetic profile, environment and previous microbial experience could influence an individual’s response, but the relative contribution, and interactions of these different factors remains largely unknown. Here, using various multi-omics, ecological and single cell approaches, we show that release of genetic inbred strains of mice, 129-SL, PWK and C57/B6 mice, to a rewilded environment and exposure of these rewilded and laboratory specific pathogen free control mice to a helminth parasite, Trichuris muris allowed us to assess the contribution and interaction of host genotype and environment to the immune cell landscape in the blood and secondary lymphoid organs. Critically, we find that the environment has the greatest effect on circulating blood immune cells while the genetic profile has the greatest effect on the mesenteric lymph node. We also observed significant interactions between the host genetic profile, environment, and infection status in their contribution to immune cell composition, with most of the effect driven by the cells of the adaptive immune system. These findings provide a model for contribution and interactions between genetics, environment, and helminth infection in the inter-individual variation of immune responses.