The emerging fungal pathogen Candida auris induces IFNγ to colonize mammalian hair follicles
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Presented at: Society for Investigative Dermatology 2025
Date: 2025-05-07 00:00:00
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Summary: Abstract Body: Public health alarm concerning the worldwide emergence of the fungus Candida auris has been fueled by its high frequency of antifungal drug resistance, including pan-resistance, and its propensity to cause deadly outbreaks. Persistent skin colonization drives transmission and lethal sepsis although its basis remains mysterious. Using a skin colonization model in mice, we compared the behaviors of C. auris and its commensal relative C. albicans. We quantified skin fungal replication/survival and distribution, immune composition, and immune cell positioning. C. auris displays a considerably higher propensity to colonize hair follicles and avidly binds to human hair. While C. albicans triggers an effective sterilizing type 3/17 antifungal immune response driven by IL-17A/F-producing lymphocytes, C. auris triggers a type 1 immune response, including expansion of IFNγ-producing lymphocytes around hair follicles. Rather than promoting fungal clearance, IFNγ promotes C. auris skin colonization by acting directly on keratinocytes. Induced IFNγ impairs epithelial barrier integrity and represses antifungal defense programs in hair follicle keratinocytes. Our data reveal that C. auris exploits focal skin immune responses to create a niche for persistence in hair follicles. Eric D. Merrill<sup>1</sup>, Victoria Prudent<sup>2</sup>, Parna Moghadam<sup>4</sup>, Abram Rodriguez<sup>3</sup>, Charlotte Hurabielle<sup>5</sup>, Elina Wells<sup>3</sup>, Pauline Basso<sup>2</sup>, Tiffany Scharschmidt<sup>1</sup>, Michael Rosenblum<sup>1</sup>, Suzanne Noble<sup>2</sup>, Ari Molofsky<sup>3</sup> 1. Dermatology, University of California San Francisco, San Francisco, CA, United States. 2. Microbiology and Immunology, University of California San Francisco, San Francisco, CA, United States. 3. Laboratory Medicine, University of California San Francisco, San Francisco, CA, United States. 4. Dermatology, Assistance Publique - Hopitaux de Paris, Paris, Île-de-France, France. 5. Rheumatology, University of California San Francisco, San Francisco, CA, United States. Innate Immunity, Microbiology, and Microbiome