Kupffer cells hasten resolution of liver immunopathology in mouse models of viral hepatitis

Giovanni Sitia, Matteo Iannacone, Roberto Aiolfi, Masanori Isogawa, Nico van Rooijen, Cristina Scozzesi, Marco E. Bianchi, Ulrich H. von Andrian, Francis V. Chisari, Luca G. Guidotti

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article numbere1002061
JournalPLoS Pathogens
Volume7
Issue number6
DOIs
Publication statusPublished - Jun 2011

ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology

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