Host and microbe adaptation underlying true fungal commensalism

Abstract

Abstract Fungi are found ubiquitously in the mammalian gut however the role of commensal fungi in the host is poorly understood. Laboratory mice are used to model host-fungi interactions however due to ultra-clean housing they do not harbor fungi. The human commensal fungus Candida albicans is widely studied to dissect host-commensal fungi interactions however prior dysbiosis of commensal bacteria is required to colonize laboratory mice. Insights from such forced host-fungal interactions are unsuitable for extrapolating mechanisms underlying fungal commensalism and its breakdown. To discover the natural fungal commensal of mice, we used pet-store “dirty” mice. We found that pet-store mice have a high fungal burden in their feces and their gut is predominantly colonized by single species of fungus, Kazachstania pintolopesii. Furthermore, we found that K. pintolopesii isolated from pet-store mice, stably colonized laboratory mice to high levels in the presence of an intact immune system and commensal bacteria. Laboratory mice colonized with K. pintolopesii exhibited increased neutrophil frequency in blood but did not show any pathological symptoms. Surprisingly, even a systemic K. pintolopesii challenge did not show any pathology in laboratory mice indicating unique adaptations of this fungus to the murine host. Remarkably, we found that laboratory mice stably colonized with K. pintolopesii are significantly protected from systemic C. albicans challenge suggesting that commensal fungi promote systemic antifungal responses in their host. In summary, our work established a novel unmanipulated murine model of fungal commensalism and provide unique insight into cellular and molecular mechanisms of mammalian host and fungal mutualism. This research was supported by grants from NIH (R01 DK113265), Searle Scholars program, and AAI Careers in Immunology Fellowship.