Fungal symbiont transmitted by free-living mice promotes type 2 immunity

• 成果类型: Article
• 署名作者: Liao, Yun; Gao, Iris H.; Kusakabe, Takato; Lin, Woan-Yu; Grier, Alexander; Pan, Xiangyu; Morzhanaeva, Olga; Shea, Terrance P.; Yano, Hiroshi; Karo-Atar, Danielle; Olsen, Kaitlin A.; Oh, Ji Hoon; Vandegrift, Kurt J.; King, Irah L.; Cuomo, Christina A.; Artis, David; Rehermann, Barbara; Lipman, Neil; Iliev, Iliyan D.
• 署名单位: Cornell University; Weill Cornell Medicine; Cornell University; Weill Cornell Medicine; Cornell University; Weill Cornell Medicine; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Cornell University; Weill Cornell Medicine; Cornell University; Weill Cornell Medicine; McGill University; McGill University; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK); Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; Brown University; Memorial Sloan Kettering Cancer Center; Cornell University; Weill Cornell Medicine
• 刊物名称: Nature
• ISSN/ISSBN: 0028-5001
• DOI: 10.1038/s41586-024-08213-2
• 发表日期: 2024-12-19
• 关键词: gut mycobiota; food allergy; mast-cells; th17 cells; commensal; pathogen; induction; performance; activation; expression

摘要

The gut mycobiota is crucial for intestinal homeostasis and immune function1. 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. Kazachstania pintolopesii is a highly prevalent fungal symbiont that can trigger type 2 immunity and influence the composition of the gut mycobiome, as well as immune and disease phenotypes.