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

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; Tatiana Kisseleva; Salomé LeibundGut-Landmann; Petra Bacher; Peter Stärkel; Bernd Schnabl

doi:10.1016/j.chom.2023.02.001

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.

Authors

Suling Zeng¹, Elisa Rosati², Carina Saggau², Berith Messner², Huikuan Chu³, Yi Duan³, Phillipp Hartmann⁴, Yanhan Wang¹, Shengyun Ma⁵, Wendy Jia Men Huang⁵, Jihyung Lee³, Sung Min Lee³, Raquel Carvalho-Gontijo³, Vivian Zhang³, Joseph P Hoffmann⁶, Jay K Kolls⁶, Eyal Raz³, David A Brenner³, Tatiana Kisseleva⁷, Salomé LeibundGut-Landmann⁸, Petra Bacher², Peter Stärkel⁹, Bernd Schnabl¹⁰

Affiliations

¹ Department of Medicine, University of California, San Diego, La Jolla, CA, USA; Department of Medicine, VA San Diego Healthcare System, San Diego, CA, USA.
² Institute of Immunology & Institute of Clinical Molecular Biology, Christian-Albrechts Universität zu Kiel and Universitätsklinik Schleswig-Holstein, Kiel, Germany.
³ Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
⁴ Department of Medicine, University of California, San Diego, La Jolla, CA, USA; Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA; Division of Gastroenterology, Hepatology & Nutrition, Rady Children's Hospital San Diego, San Diego, CA, USA.
⁵ Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
⁶ Center for Translational Research in Infection and Inflammation, Department of Pediatrics and Department of Medicine, Tulane University School of Medicine, New Orleans, LA, USA.
⁷ Department of Surgery, University of California, San Diego, La Jolla, CA, USA.
⁸ Section of Immunology, Vetsuisse Faculty, University of Zürich, Zürich, Switzerland; Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland.
⁹ St. Luc University Hospital, Université Catholique de Louvain, Brussels, Belgium.
¹⁰ Department of Medicine, University of California, San Diego, La Jolla, CA, USA; Department of Medicine, VA San Diego Healthcare System, San Diego, CA, USA. Electronic address: beschnabl@health.ucsd.edu.

Abstract

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.

Keywords: ALD; alcoholic liver disease; microbiome; microbiota; mycobiome.

Published by Elsevier Inc.

MeSH terms

Animals
Candida
Candida albicans*
Ethanol / toxicity
Mice
Mice, Transgenic
Th17 Cells*

Substances

Ethanol

Abstract

MeSH terms

Substances

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