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

Publication

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

Journal Paper/Review - Mar 1, 2010

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

Citation

Lang P, Zinkernagel R, Ohashi P, Häussinger D, Harris N, Hengartner H, Ludewig B, Kalinke U, Van Rooijen N, Cervantes-Barragan L, Kulawik A, Meryk A, Krings C, Gailus N, Borkens S, Scheu S, Honke N, Recher M, Lang K. Tissue macrophages suppress viral replication and prevent severe immunopathology in an interferon-I-dependent manner in mice. Hepatology 2010; 52:25-32.

Type

Journal Paper/Review (English)

Journal

Hepatology 2010; 52

Publication Date

Mar 1, 2010

Issn Electronic

1527-3350

Pages

25-32

Brief description/objective

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. (HEPATOLOGY 2010).