美国康奈尔大学Iliyan D. Iliev团队发现，自由生活的小鼠传播的真菌共生体促进2型免疫。2024年11月27日，《自然》杂志在线发表了这项成果。

研究人员表明，Kazachstania pintolopesii是真菌共生体，在野生城市和乡村小鼠中具有卓越的定植能力，并能够在小鼠胃肠道内定殖并主导肠道真菌组。K. pintolopesii的定殖以不依赖细菌的方式进行，能够增强对其他真菌的定殖抗性，并避免宿主免疫监视，从而维持共生状态。在黏膜环境变化后，K. pintolopesii定殖触发了小鼠的2型免疫反应，并引起胃肠道嗜酸性粒细胞增多。

机制上，研究人员发现K. pintolopesii通过诱导上皮细胞IL-33及其下游IL-33–ST2信号通路，在黏液波动期间激活2型免疫。K. pintolopesii诱导的2型免疫增强了对寄生虫感染的抵抗力，或在特定环境下加剧了胃肠道过敏。

该研究表明，K. pintolopesii是小鼠的共生菌，并为研究肠道真菌共生和宿主免疫提供了宝贵的模型生物。其在小鼠中未被注意到的存在，突显了需要评估其对实验结果和表型的影响。

据了解，肠道真菌群对于肠道稳态和免疫功能至关重要。然而，其变异性以及实验室小鼠中真菌定植的不一致性，妨碍了研究支持共生关系的演化和免疫过程。

附：英文原文

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

Author: 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.

Issue&Volume: 2024-11-27

Abstract: 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.

DOI: 10.1038/s41586-024-08213-2

Source: https://www.nature.com/articles/s41586-024-08213-2