Candida albicans-specific Th17 cell-mediated response contributes to alcohol-associated liver disease
(2023) Cell Host & Microbe — Vol. 31, n° 3, p. 389-404 (2023)
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- (en) Alcohol-associated liver disease is accompanied by intestinal mycobiome dysbiosis, yet the impacts on liver disease are unclear. We demonstrate that Candida albicans-specific T helper 17 (Th17) cells are increased in circulation and present in the liver of patients with alcohol-associated liver disease. Chronic ethanol administration in mice causes migration of Candida albicans (C. albicans)-reactive Th17 cells from the intestine to the liver. The antifungal agent nystatin decreased C. albicans-specific Th17 cells in the liver and reduced ethanol-induced liver disease in mice. Transgenic mice expressing T cell receptors (TCRs) reactive to Candida antigens developed more severe ethanol-induced liver disease than transgene-negative littermates. Adoptively transferring Candida-specific TCR transgenic T cells or polyclonal C. albicans-primed T cells exacerbated ethanol-induced liver disease in wild-type mice. Interleukin-17 (IL-17) receptor A signaling in Kupffer cells was required for the effects of polyclonal C. albicans-primed T cells. Our findings indicate that ethanol increases C. albicans-specific Th17 cells, which contribute to alcohol-associated liver disease.
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Zeng, S., Rosati, E., Saggau, C., Messner, B., Chu, H., Duan, Y., Hartmann, P., Wang, Y., Ma, S., Huang, W. J. M., Lee, J., Lee, S. M., Carvalho-Gontijo, R., Zhang, V., Hoffmann, J. P., Kolls, J. K., Raz, E., Brenner, D. A., Kisseleva, T., et al. (2023). Candida albicans-specific Th17 cell-mediated response contributes to alcohol-associated liver disease. Cell Host & Microbe, 31(3), 389-404. https://doi.org/10.1016/j.chom.2023.02.001 (Original work published 2023)