期刊
PLOS PATHOGENS
卷 7, 期 6, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.ppat.1002061
关键词
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资金
- NIH [R01-AI40696, R01-AI20001, R01-CA40489, R01-AI079060]
- Italian Association for Cancer Research (AIRC) [4643, 6278]
- European Research Council (ERC) [250219]
- Istituto Superiore di Sanita' (Italy) [50G.36]
- Ministero della Salute (Italy) [GR08.17]
- European Community [MC-IRG-2010-268129]
- Giovanni-Armenise Harvard Foundation
Kupffer cells (KCs) are widely considered important contributors to liver injury during viral hepatitis due to their proinflammatory 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.
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