Kupffer Cells Hasten Resolution of Liver Immunopathology in Mouse Models of Viral Hepatitis
Year: 2011
Type: article
Abstract: Kupffer cells (KCs) are widely considered important contributors to liver injury during viral hepatitis due to their pro-inflammatory activity. Herein we utilized hepatitis B virus (HBV)-replication competent transgenic mice and wild-type mice infected with a hepatotropic adenovirus to demonstrate that KCs do not directly induce hepatocellular injury nor do they affect the pathogenic potential of virus-specific CD8 T cells. Instead, KCs limit the severity of liver immunopathology. Mechanistically, our results are most compatible with the hypothesis that KCs contain liver immunopathology by removing apoptotic hepatocytes in a manner largely dependent on scavenger receptors. Apoptotic hepatocytes not readily removed by KCs become secondarily necrotic and release high-mobility group box 1 (HMGB-1) protein, promoting organ infiltration by inflammatory cells, particularly neutrophils. Overall, these results indicate that KCs resolve rather than worsen liver immunopathology.
Source: PLoS Pathogens
Language: English
Subfield: Hepatology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,043
Awards: Imaging liver immunopathology by intravital microscopy, Pathogenesis of Liver Disease in Hepatitis, Pathogenesis of Hepatitis B Virus in Transgenic Mice, Immunological Priming to Hepatitis B Virus, Imaging liver immunopathology by intravital microscopy (IVM): a new approach to study the pathogenesis of hepatitis B virus (HBV) infection, Regulation of HBV Replication by the Immune System
OpenAlex ID: W1964879847