Laboratory mice exposed naturally to multiple pathogens show profound sex- and organ-dependent immunological phenotypes 3149

Abstract Description Rationale Mice are used for models of human diseases. The immune cell composition of specific-pathogen-free (SPF) mice closely resembles that of newborn humans. Adult humans have been exposed to a multitude of pathogens throughout their lives. In this project, we sought to create a mouse model resembling humans by co-housing SPF mice to pet store mice. Methods Male and Female SPF B6 mice were co-housed with pet store mice. Multiplexed PCR was used to assess pathogen transmission. After 2 months, lungs, small intestines, and colons were analyzed by high-dimensional mass cytometry and multiplexed cytokine assay. Results Co-housed male mice frequently succumbed to infection. After two months, co-housed males still exhibited signs of active infection across all organs examined including profound myeloid and T effector cell infiltration. In female mice, infection was less fatal and active sickness resolved by two months. Across tissues, T cells exhibited both memory and effector phenotypes. Increases in monocytes and granulocytes were observed in lungs and colons while CD8+ T cells increased in the small intestine. Importantly, innate lymphoid cells were not displaced but underwent phenotypic changes. Conclusion Asynchronous systemic exposure to multiple pathogens in mice results in dramatic alterations to the immune landscape in a sex- and tissue-dependent manner. When used in disease models, these mice may provide new insight beyond those obtained previously with SPF mice. Funding Sources •NIAID R37 AL71106 Topic Categories Mucosal and Regional Immunology (MUC)