IL-17-mediated antifungal immunity restricts Candida albicans pathogenicity in the oral cavity.

Abstract

Candida albicans is a common resident of the microbiota that supports host homeostasis but can cause disease when immune defences are impaired. Mucocutaneous candidiasis in individuals with IL-17 immune defects provides insights into the immune system's role in controlling C. albicans. Here, using a murine model of oral colonization, we show that IL-17 signalling maintains C. albicans in a non-pathogenic state. Loss of IL-17 leads to fungal filamentation and upregulation of hyphae-associated genes, which is accompanied by epithelial barrier disruption and inflammation, linked to aberrant IL-22 and IL-13 production. The emergence of pathogenic fungal traits was associated with impaired zinc chelation due to reduced calprotectin expression in the IL-17-deficient mice. Prolonged exposure to the immune-dysregulated tissue led to selection of stable, damage-inducing C. albicans variants, mirroring the evolution of isolates from a chronic mucocutaneous candidiasis patient. These findings reveal how IL-17 protects against fungal pathogenicity and how immune dysfunction fosters C. albicans adaptation and diversification within the host.