Candida albicans-specific Th17 cell-mediated response contributes to alcohol-associated liver disease

Zeng, Suling Rosati, Elisa Saggau, Carina Messner, Berith Chu, Huikuan Duan, Yi Hartmann, Phillipp Wang, Yanhan Ma, Shengyun Huang, Wendy Jia Men Lee, Jihyung Lee, Sung Min Carvalho-Gontijo, Raquel Zhang, Vivian Hoffmann, Joseph P. Kolls, Jay K. Raz, Eyal Brenner, David A. Kisseleva, Tatiana LeibundGut-Landmann, Salomé Bacher, Petra Starkel, Peter [UCL] Schnabl, Bernd et al.[show all]

(eng) 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.