Human but not mouse hepatocytes respond to interferon-lambda in vivo.
The type III interferon (IFN) receptor is preferentially expressed by epithelial cells. It is made of two subunits: IFNLR1, which is specific to IFN-lambda (IFN-λ) and IL10RB, which is shared by other cytokine receptors. Human hepatocytes express IFNLR1 and respond to IFN-λ. In contrast, the IFN-λ response of the mouse liver is very weak and IFNLR1 expression is hardly detectable in this organ. Here we investigated the IFN-λ response at the cellular level in the mouse liver and we tested whether human and mouse hepatocytes truly differ in responsiveness to IFN-λ. When monitoring expression of the IFN-responsive Mx genes by immunohistofluorescence, we observed that the IFN-λ response in mouse livers was restricted to cholangiocytes, which form the bile ducts, and that mouse hepatocytes were indeed not responsive to IFN-λ. The lack of mouse hepatocyte response to IFN-λ was observed in different experimental settings, including the infection with a hepatotropic strain of influenza A virus which triggered a strong local production of IFN-λ. With the help of chimeric mice containing transplanted human hepatocytes, we show that hepatocytes of human origin readily responded to IFN-λ in a murine environment. Thus, our data suggest that human but not mouse hepatocytes are responsive to IFN-λ in vivo. The non-responsiveness is an intrinsic property of mouse hepatocytes and is not due to the mouse liver micro-environment.
de Duve Institute, Université Catholique de Louvain, Brussels, Belgium.
Pascale
P
Hermant
de Duve Institute, Université Catholique de Louvain, Brussels, Belgium.
Céline
C
Demarez
Institute for Virology, University Medical Center Freiburg, Freiburg, Germany ; Spemann Graduate School of Biology and Medicine (SGBM), University Medical Center Freiburg, Freiburg, Germany.
Tanel
T
Mahlakõiv
Institute for Virology, University Medical Center Freiburg, Freiburg, Germany.
Peter
P
Staeheli
Center for Vaccinology, Department of Clinical Chemistry, Microbiology and Immunology, Ghent University and Hospital, Ghent, Belgium.
Philip
P
Meuleman
de Duve Institute, Université Catholique de Louvain, Brussels, Belgium.
Thomas
T
Michiels
D000818:Animals; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D016513:Mice, SCID; D008822:Mice, Transgenic; D018121:Receptors, Cytokine; D017471:Receptors, Interferon / Q000235:genetics / Q000378:metabolism*; D013045:Species Specificity; D000095022:Interferon Lambda
D007372:Interferons; D007378:Interleukins; D018121:Receptors, Cytokine; D017471:Receptors, Interferon; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C579640:IFNLR1 protein, human; C000604340:IFNLR1 protein, mouse