title: Tissue macrophages suppress viral replication and prevent severe immunopathology in an interferon-I-dependent manner in mice.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Experimental Immunology, University Hospital of Zurich, Zurich, Switzerland. philipp.lang@gmx.net
authors.forename: Philipp A
authors.initials: PA
authors.lastname: Lang
authors.forename: Mike
authors.initials: M
authors.lastname: Recher
authors.forename: Nadine
authors.initials: N
authors.lastname: Honke
authors.forename: Stefanie
authors.initials: S
authors.lastname: Scheu
authors.forename: Stephanie
authors.initials: S
authors.lastname: Borkens
authors.forename: Nicole
authors.initials: N
authors.lastname: Gailus
authors.forename: Caroline
authors.initials: C
authors.lastname: Krings
authors.forename: Andreas
authors.initials: A
authors.lastname: Meryk
authors.forename: Andreas
authors.initials: A
authors.lastname: Kulawik
authors.forename: Luisa
authors.initials: L
authors.lastname: Cervantes-Barragan
authors.forename: Nico
authors.initials: N
authors.lastname: Van Rooijen
authors.forename: Ulrich
authors.initials: U
authors.lastname: Kalinke
authors.forename: Burkhard
authors.initials: B
authors.lastname: Ludewig
authors.forename: Hans
authors.initials: H
authors.lastname: Hengartner
authors.forename: Nicola
authors.initials: N
authors.lastname: Harris
authors.forename: Dieter
authors.initials: D
authors.lastname: Häussinger
authors.forename: Pamela S
authors.initials: PS
authors.lastname: Ohashi
authors.forename: Rolf M
authors.initials: RM
authors.lastname: Zinkernagel
authors.forename: Karl S
authors.initials: KS
authors.lastname: Lang
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D006505:Hepatitis / Q000276:immunology* / Q000473:pathology / Q000821:virology; D007154:Immune System Diseases / Q000276:immunology*; D007370:Interferon Type I / Q000276:immunology*; D007728:Kupffer Cells / Q000276:immunology*; D008099:Liver / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D014779:Virus Replication
chemical_list: D007370:Interferon Type I