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

Cell Host Microbe. 2023 Mar 8;31(3):389-404.e7. doi: 10.1016/j.chom.2023.02.001.ABSTRACTAlcohol-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.PMID:36893735 | DOI:10.1016/j.chom.2023.02.001

Source: Cell Host and Microbe - March 9, 2023 Category: Microbiology Authors: Suling Zeng Elisa Rosati Carina Saggau Berith Messner Huikuan Chu Yi Duan Phillipp Hartmann Yanhan Wang Shengyun Ma Wendy Jia Men Huang Jihyung Lee Sung Min Lee Raquel Carvalho-Gontijo Vivian Zhang Joseph P Hoffmann Jay K Kolls Eyal Raz David A Brenner Ta Source Type: research