The fungal pathogen Candida auris exposes chitin to trigger IFNγ and persist in hair follicles.

Candida auris is a multidrug-resistant fungus of major public health concern whose mechanisms for persistence on skin, a major risk factor for deadly outbreaks, remain unclear. In this study, we compared skin colonization by C. auris versus C. albicans to illuminate distinct fungal-immune interactions in mice. C. auris exhibited enhanced skin persistence, hair follicle tropism, and direct hair binding. Whereas C. albicans triggered a type 3/17-skewed sterilizing antifungal immune response, C. auris triggered a type 1 interferon-γ (IFNγ)-driven response directed toward hair follicles. IFNγ enhanced C. auris colonization by signaling to keratinocytes and repressing epithelial antifungal defense programs. Genetic and biochemical approaches demonstrated that, in response to cues associated with the skin, C. auris increases cell wall chitin exposure, triggering type 1 immunity and promoting fungal persistence.