Tissue macrophages suppress viral replication and prevent severe immunopathology in an interferon-I-dependent manner in mice.
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.
Lang
Philipp A
PA
Institute of Experimental Immunology, University Hospital of Zurich, Zurich, Switzerland. philipp.lang@gmx.net
Recher
Mike
M
Honke
Nadine
N
Scheu
Stefanie
S
Borkens
Stephanie
S
Gailus
Nicole
N
Krings
Caroline
C
Meryk
Andreas
A
Kulawik
Andreas
A
Cervantes-Barragan
Luisa
L
Van Rooijen
Nico
N
Kalinke
Ulrich
U
Ludewig
Burkhard
B
Hengartner
Hans
H
Harris
Nicola
N
Häussinger
Dieter
D
Ohashi
Pamela S
PS
Zinkernagel
Rolf M
RM
Lang
Karl S
KS
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
D007370:Interferon Type I