1. Fungal symbiont transmitted by free-living mice promotes type 2 immunity.
- Author
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Liao Y, Gao IH, Kusakabe T, Lin WY, Grier A, Pan X, Morzhanaeva O, Shea TP, Yano H, Karo-Atar D, Olsen KA, Oh JH, Vandegrift KJ, King IL, Cuomo CA, Artis D, Rehermann B, Lipman N, and Iliev ID
- Subjects
- Animals, Female, Male, Mice, Eosinophilia immunology, Eosinophilia microbiology, Gastrointestinal Tract microbiology, Gastrointestinal Tract immunology, Mice, Inbred C57BL, Mycobiome immunology, Mice, Knockout, Mice, Inbred BALB C, Interleukin-1 Receptor-Like 1 Protein immunology, Gastrointestinal Microbiome immunology, Interleukin-33 immunology, Symbiosis immunology, Saccharomycetales physiology, Immunity
- Abstract
The gut mycobiota is crucial for intestinal homeostasis and immune function
1 . Yet its variability and inconsistent fungal colonization of laboratory mice hinders the study of the evolutionary and immune processes that underpin commensalism2,3 . Here, we show that Kazachstania pintolopesii is a fungal commensal in wild urban and rural mice, with an exceptional ability to colonize the mouse gastrointestinal tract and dominate the gut mycobiome. Kazachstania pintolopesii colonization occurs in a bacteria-independent manner, results in enhanced colonization resistance to other fungi and is shielded from host immune surveillance, allowing commensal presence. Following changes in the mucosal environment, K. pintolopesii colonization triggers a type 2 immune response in mice and induces gastrointestinal eosinophilia. Mechanistically, we determined that K. pintolopesii activates type 2 immunity via the induction of epithelial IL-33 and downstream IL-33-ST2 signalling during mucus fluctuations. Kazachstania pintolopesii-induced type 2 immunity enhanced resistance to helminth infections or aggravated gastrointestinal allergy in a context-dependent manner. Our findings indicate that K. pintolopesii is a mouse commensal and serves as a valuable model organism for studying gut fungal commensalism and immunity in its native host. Its unnoticed presence in mouse facilities highlights the need to evaluate its influence on experimental outcomes and phenotypes., Competing Interests: Competing interests: I.D.I. has participated in discussion with Moderna, Inc. D.A. has contributed to scientific advisory boards at Pfizer, Takeda, FARE and the KRF. B.R. and J.H.O. disclose that NIDDK has a Collaborative Research Agreement and Development Award with Genentech and granted a licence on WildR mice to Taconic Biosciences. The other authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)- Published
- 2024
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