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The role of liver macrophages in viral liver pathogenesis
Journal article   Open access   Peer reviewed

The role of liver macrophages in viral liver pathogenesis

Alexis Brantly, Kyle Yeakle, Michael Bouchard, Peter J Gaskill and Michael R Nonnemacher
Journal of leukocyte biology, v 117(9), qiaf088
25 Jun 2025
PMID: 40561105
url
https://doi.org/10.1093/jleuko/qiaf088View
Published, Version of Record (VoR) Open

Abstract

Kupffer cell HIV HCC HCV fibrosis HBV Macrophage
Liver macrophages play important roles in the pathophysiology of liver fibrosis and hepatocellular carcinoma (HCC). However, liver macrophages are a heterogenous population and have differing roles in maintenance of liver function and response in disease. In a healthy liver, macrophages play a critical role in antigen processing, maintaining tolerance to the high levels of gut-derived bacterial products, and regulating inflammation through cytokine response. However, macrophages also play a critical role in liver pathology, specifically in the context of viral infection. The liver is targeted by multiple viruses, including human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV), which dysregulate macrophage functions to affect liver disease. Infection with any of these viruses is associated with increased risk of developing HCC, and co-infection further accelerates the progression to liver disease and cancer. However, the exact mechanisms by which liver macrophages contribute to disease in the context of viral infections are not well defined. This is a particularly acute issue in HIV-infected populations, which have high incidence of HBV- and HCV-coinfection. To address this knowledge gap, this review describes the populations of macrophages in the liver, outlines the current models and limitations associated with the study of liver macrophages, discusses the function and role of liver macrophages in the context of viral infection, and describes the mechanisms by which these cells contribute to HCC and fibrosis. We then use this information to propose focus areas for the liver macrophage field to better address and resolve viral liver disease.

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Collaboration types
Domestic collaboration
Web of Science research areas
Cell Biology
Hematology
Immunology
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