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- W4385686180 abstract "Abstract Interferon-gamma (IFNγ) is a powerful cytokine that is crucial for adequate host defense. However, unchecked IFNγ can cause autoimmunity in several organs and can be directly toxic to host cells. Indeed, excessive IFNγ, or type II interferonopathy, occurs in several diverse disease states, including STAT1 gain-of-function mutations, autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), Downs syndrome, and AIDS. We have recently shown that in APECED, which is caused by deficiency of autoimmune regulator (AIRE), excessive IFNγ leads to greater susceptibility to oral Candida albicans infection. C. albicans is both a normal member of the human microbiome and the most common human fungal pathogen. The ability of C. albicans to morph between commensal and pathogenic states is tied to its complex transcriptional regulation of virulence traits in response to environmental cues. Thus, we hypothesize that excessive IFNγ in the oral mucosa leads C. albicans to transition to a more virulent state. We are using transcriptomics to define the response of C. albicans to excess IFNγ. Further, we have found that during infection of oral epithelial cells, C. albicans becomes more invasive in the presence of IFNγ. Thus, we are also using metabolomics to investigate soluble mediators released by these cells in response to IFNγ. These experiments will shed light on C. albicans virulence regulation in response to autoinflammatory conditions. Further, this study will provide new insights into the dualistic nature of IFNγ — providing protection against many pathogens, while facilitating disease from a specific pathogen. This work was supported by the Division of Intramural Research of the NIAID (ZIA AI001175)." @default.
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- W4385686180 date "2023-05-01" @default.
- W4385686180 modified "2023-09-27" @default.
- W4385686180 title "<i>Candida albicans</i>pathogenesis in the context of mucosal type II interferonopathy" @default.
- W4385686180 doi "https://doi.org/10.4049/jimmunol.210.supp.82.13" @default.
- W4385686180 hasPublicationYear "2023" @default.
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