A host-adapted commensal fungus from pet store mice drives type 2 immunity and cross-kingdom protection.

To better mimic natural immunity, researchers utilize naturalized, wilded, wildling, and dirty/pet store mouse models with natural microbial exposure. This study screened the gut mycobiome of pet store mice and identified Kazachstania pintolopesii as a dominant, widespread fungus. The isolated K. pintolopesii stably colonizes the gastrointestinal tract of laboratory mice independently of bacterial composition, outcompeting non-murine fungal strains. Unlike C. albicans colonization, K. pintolopesii did not induce circulating neutrophil expansion or T helper 17 cells (Th17) cell populations in the gut mucosa. Adaptive immune deficiency (Rag1 knockout mice) did not affect K. pintolopesii colonization or host response. Instead, it selectively triggers a strong type 2 mucosal immune response, increasing tuft and goblet cells and stimulating T helper 2 (Th2) and group 2 innate lymphoid cell (ILC2) populations. This immune profile confers notable protection against intestinal nematode infection. Altogether, K. pintolopesii serves as an exemplary commensal mycobiota model, revealing distinct mechanisms for host tolerance and immune modulation.