Interferon-lambda contributes to innate immunity of mice against influenza A virus but not against hepatotropic viruses

PLoS Pathog. 2008 Sep 12;4(9):e1000151. doi: 10.1371/journal.ppat.1000151.


Virus-infected cells secrete a broad range of interferon (IFN) subtypes which in turn trigger the synthesis of antiviral factors that confer host resistance. IFN-alpha, IFN-beta and other type I IFNs signal through a common universally expressed cell surface receptor, whereas IFN-lambda uses a distinct receptor complex for signaling that is not present on all cell types. Since type I IFN receptor-deficient mice (IFNAR1(0/0)) exhibit greatly increased susceptibility to various viral diseases, it remained unclear to which degree IFN-lambda might contribute to innate immunity. To address this issue we performed influenza A virus infections of mice which carry functional alleles of the influenza virus resistance gene Mx1 and which, therefore, develop a more complete innate immune response to influenza viruses than standard laboratory mice. We demonstrate that intranasal administration of IFN-lambda readily induced the antiviral factor Mx1 in mouse lungs and efficiently protected IFNAR1(0/0) mice from lethal influenza virus infection. By contrast, intraperitoneal application of IFN-lambda failed to induce Mx1 in the liver of IFNAR1(0/0) mice and did not protect against hepatotropic virus infections. Mice lacking functional IFN-lambda receptors were only slightly more susceptible to influenza virus than wild-type mice. However, mice lacking functional receptors for both IFN-alpha/beta and IFN-lambda were hypersensitive and even failed to restrict usually non-pathogenic influenza virus mutants lacking the IFN-antagonistic factor NS1. Interestingly, the double-knockout mice were not more susceptible against hepatotropic viruses than IFNAR1(0/0) mice. From these results we conclude that IFN-lambda contributes to inborn resistance against viral pathogens infecting the lung but not the liver.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokines / immunology
  • Cytokines / pharmacology*
  • GTP-Binding Proteins / immunology
  • Hepatovirus / immunology
  • Immunity, Innate / drug effects*
  • Influenza A virus / immunology*
  • Lung / virology
  • Mice
  • Mice, Knockout
  • Myxovirus Resistance Proteins
  • Orthomyxoviridae Infections / drug therapy
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / prevention & control
  • Receptors, Interferon / deficiency
  • Receptors, Interferon / immunology


  • Cytokines
  • Mx1 protein, mouse
  • Myxovirus Resistance Proteins
  • Receptors, Interferon
  • interferon-lambda protein, mouse
  • GTP-Binding Proteins