Ambiguous Pathogenic Roles of Macrophages in Alcohol-Associated Liver Diseases

Abstract

Yeni Ait Ahmed,1 Fouad Lafdil,2– 4 Frank Tacke1 1Department of Hepatology & Gastroenterology, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum (CVK) and Campus Charité Mitte (CCM), Berlin, Germany; 2Université Paris-Est, UMR-S955, UPEC, Créteil, France; 3Institut National de la Sante et de la Recherche Medicale (INSERM), U955, Créteil, France; 4Institut Universitaire de France (IUF), Paris, FranceCorrespondence: Frank Tacke, Charité - Universitätsmedizin Berlin, Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum (CVK) and Campus Charité Mitte (CCM), Augustenburger Platz 1, D-13353, Berlin, Germany, Tel [phone], Fax [phone], Email [email protected]: Alcohol-associated liver disease (ALD) represents a major public health issue worldwide and is a leading etiology of liver cirrhosis. Alcohol-related liver injuries include a range of manifestations including alcoholic hepatitis (AH), simple steatosis, steatohepatitis, hepatic fibrosis, cirrhosis and liver cancer. Liver disease occurs from several pathological disturbances such as the metabolism of ethanol, which generates reactive oxygen species (ROS) in hepatocytes, alterations in the gut microbiota, and the immune response to these changes. A common hallmark of these liver affections is the establishment of an inflammatory environment, and some (broad) anti-inflammatory approaches are used to treat AH (eg, corticosteroids). Macrophages, which represent the main innate immune cells in the liver, respond to a wide variety of (pathogenic) stimuli and adopt a large spectrum of phenotypes. This translates to a diversity of functions including pathogen and debris clearance, recruitment of other immune cells, activation of fibroblasts, or tissue repair. Thus, macrophage populations play a crucial role in the course of ALD, but the underlying mechanisms driving macrophage polarization and their functionality in ALD are complex. In this review, we explore the various populations of hepatic macrophages in alcohol-associated liver disease and the underlying mechanisms driving their polarization. Additionally, we summarize the crosstalk between hepatic macrophages and other hepatic cell types in ALD, in order to support the exploration of targeted therapeutics by modulating macrophage polarization.Keywords: macrophages, alcohol, liver disease, fibrosis, cirrhosis

Keywords

• macrophages
• alcohol
• liver disease
• fibrosis
• cirrhosis