Human but Not Mouse Hepatocytes Respond to Interferon-Lambda In Vivo

• Published in: PloS one Vol. 9; no. 1; p. e87906
• Main Authors: Hermant, Pascale, Demarez, Céline, Mahlakõiv, Tanel, Staeheli, Peter, Meuleman, Philip, Michiels, Thomas
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 31.01.2014; Public Library of Science (PLoS)
• Subjects: Animals; Bile ducts; Biological response modifiers; Biology; Cloning; Cytokine receptors; Environmental monitoring; Epithelial cells; Gene expression; Health aspects; Hepatitis; Hepatocytes; Hepatocytes - cytology; Hepatocytes - metabolism; Hepatology; Humans; Infections; Influenza; Influenza A; Interferon; Interferons; Interleukin 1; Interleukins - genetics; Interleukins - metabolism; Liver; Liver - cytology; Liver - metabolism; Medical research; Medicine; Mice; Mice, SCID; Mice, Transgenic; Plasmids; Proteins; Receptors; Receptors, Cytokine; Receptors, Interferon - genetics; Receptors, Interferon - metabolism; Rodents; Species Specificity; Transgenic animals; Viral infections; Virology; Viruses; Belgium; Germany
• DOI: 10.1371/journal.pone.0087906
• ISSN: 1932-6203

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.