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bioRxiv · 10.1101/2022.02.07.479457

Deep tissue infection by an invasive human fungal pathogen requires novel lipid-based suppression of the IL-17 response

Basso, P.·Dang, E. V.·Urisman, A.·Madhani, H. D.·Cowen, L. E.·Noble, S. M.
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Abstract

Candida albicans is the most common cause of human fungal infection, but the mechanisms of invasive pathogenesis remain poorly defined. Here we identify an unexpected mechanism: lipid-mediated immunosuppression. Through forward genetics, we found that C. albicans secretes a lipase, Lip2, that is critical for invasive disease. Murine infection with C. albicans strains that lack Lip2 display an exaggerated host IL-17 response that leads to fungal clearance from solid organs and host survival. IL-17 signaling is required for Lip2 action. The lipase activity of Lip2 inhibits IL-17 production indirectly through suppression of IL-23 production by tissue resident dendritic cells. We conclude that C. albicans suppresses antifungal IL-17 defense in solid organs by altering the tissue lipid milieu.

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Basso, P., Dang, E. V., Urisman, A., Madhani, H. D., Cowen, L. E., Noble, S. M.. 2022-02-08. Deep tissue infection by an invasive human fungal pathogen requires novel lipid-based suppression of the IL-17 response. https://doi.org/10.1101/2022.02.07.479457

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