<i>Candida albicans</i>pathogenesis in the context of mucosal type II interferonopathy

Abstract Interferon-gamma (IFNγ) is a powerful cytokine that crucial for adequate host defense. However, unchecked IFNγ can cause autoimmunity in several organs and be directly toxic to cells. Indeed, excessive IFNγ, or type II interferonopathy, occurs diverse disease states, including STAT1 gain-of-function mutations, autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), Downs syndrome, AIDS. We have recently shown APECED, which caused by deficiency of regulator (AIRE), leads greater susceptibility oral Candida albicans infection. C. both normal member the human microbiome most common fungal pathogen. The ability morph between commensal pathogenic states tied its complex transcriptional regulation virulence traits response environmental cues. Thus, we hypothesize mucosa transition more virulent state. are using transcriptomics define excess IFNγ. Further, found during infection epithelial cells, becomes invasive presence also metabolomics investigate soluble mediators released these cells These experiments will shed light on autoinflammatory conditions. this study provide new insights into dualistic nature — providing protection against many pathogens, while facilitating from specific This work was supported Division Intramural Research NIAID (ZIA AI001175).