Human but not mouse hepatocytes respond to interferon-lambda in vivo

PLoS One. 2014 Jan 31;9(1):e87906. doi: 10.1371/journal.pone.0087906. eCollection 2014.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Hepatocytes / cytology
  • Hepatocytes / metabolism*
  • Humans
  • Interferons
  • Interleukins / genetics
  • Interleukins / metabolism*
  • Liver / cytology
  • Liver / metabolism*
  • Mice
  • Mice, SCID
  • Mice, Transgenic
  • Receptors, Cytokine
  • Receptors, Interferon / genetics
  • Receptors, Interferon / metabolism*
  • Species Specificity

Substances

  • interferon-lambda, human
  • IFNLR1 protein, human
  • IFNLR1 protein, mouse
  • Interleukins
  • Receptors, Cytokine
  • Receptors, Interferon
  • Interferons

Grants and funding

P.H. was a research assistant with the Université catholique de Louvain (UCL). This work was supported by the National Fund for Scientific Research (FNRS-FRSM), by the Research Foundation Flanders (FWO project #3G052112), by the Ghent University (GOA #01G01712), by the Action de Recherche Concertée (ARC) of the French Community of Belgium and by the Interuniversitary Attraction Poles programme initiated by the Belgian Science Policy Office (PAI-P7/45 BELVIR and IAP-P7/47-HEPRO2). TaM was supported in part by the Excellence Initiative of the German Research Foundation (GSC-4, Spemann Graduate School). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.