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Tissue macrophages suppress viral replication and prevent severe immunopathology in an interferon-I-dependent manner in mice

✍ Scribed by Philipp A. Lang; Mike Recher; Nadine Honke; Stefanie Scheu; Stephanie Borkens; Nicole Gailus; Caroline Krings; Andreas Meryk; Andreas Kulawik; Luisa Cervantes-Barragan; Nico Van Rooijen; Ulrich Kalinke; Burkhard Ludewig; Hans Hengartner; Nicola Harris; Dieter Häussinger; Pamela S. Ohashi; Rolf M. Zinkernagel; Karl S. Lang


Book ID
102242381
Publisher
John Wiley and Sons
Year
2010
Tongue
English
Weight
470 KB
Volume
52
Category
Article
ISSN
0270-9139

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✦ Synopsis


The innate immune response plays an essential role in the prevention of early viral dissemination. We used the lymphocytic choriomeningitis virus model system to analyze the role of tissue macrophages/Kupffer cells in this process. Our findings demonstrated that Kupffer cells are essential for the efficient capture of infectious virus and for preventing viral replication. The latter process involved activation of Kupffer cells by interferon (IFN)-I and prevented viral spread to neighboring hepatocytes. In the absence of Kupffer cells, hepatocytes were not able to suppress virus replication, even in the presence of IFN-I, leading to prolonged viral replication and severe T cell-dependent immunopathology.

Conclusion:

Tissue-resident macrophages play a crucial role in early viral capture and represent the major liver cell type exhibiting responsiveness to ifn-i and providing control of viral replication.