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

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

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54 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)25-32
Number of pages8
JournalHepatology
Volume52
Issue number1
DOIs
Publication statusPublished - 1 Jul 2010
Externally publishedYes

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