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

Abstract

<i>Candida auris</i> 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 <i>C. auris</i> versus <i>C. albicans</i> to illuminate distinct fungal-immune interactions in mice. <i>C. auris</i> exhibited enhanced skin persistence, hair follicle tropism, and direct hair binding. Whereas <i>C. albicans</i> triggered a type 3/17-skewed sterilizing antifungal immune response, <i>C. auris</i> triggered a type 1 interferon-γ (IFNγ)-driven response directed toward hair follicles. IFNγ enhanced <i>C. auris</i> 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, <i>C. auris</i> increases cell wall chitin exposure, triggering type 1 immunity and promoting fungal persistence.