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An important role for type III interferon (IFN-lambda/IL-28) in TLR-induced antiviral activity.

Type III IFNs (IFN-lambda/IL-28/29) are cytokines with type I IFN-like antiviral activities, which remain poorly characterized. We herein show that most cell types expressed both types I and III IFNs after TLR stimulation or virus infection, whereas the ability of cells to respond to IFN-lambda was restricted to a narrow subset of cells, including plasmacytoid dendritic cells and epithelial cells. To examine the role of type III IFN in antiviral defense, we generated IL-28Ralpha-deficient mice. These mice were indistinguishable from wild-type mice with respect to clearance of a panel of different viruses, whereas mice lacking the type I IFN receptor (IFNAR(-/-)) were significantly impaired. However, the strong antiviral activity evoked by treatment of mice with TLR3 or TLR9 agonists was significantly reduced in both IL-28RA(-/-) and IFNAR(-/-) mice. The type I IFN receptor system has been shown to mediate positive feedback on IFN-alphabeta expression, and we found that the type I IFN receptor system also mediates positive feedback on IFN-lambda expression, whereas IL-28Ralpha signaling does not provide feedback on either type I or type III IFN expression in vivo. Finally, using bone-marrow chimeric mice we showed that TLR-activated antiviral defense requires expression of IL-28Ralpha only on nonhemopoietic cells. In this compartment, epithelial cells responded to IFN-lambda and directly restricted virus replication. Our data suggest type III IFN to target a specific subset of cells and to contribute to the antiviral response evoked by TLRs.

Pubmed ID: 18250457


  • Ank N
  • Iversen MB
  • Bartholdy C
  • Staeheli P
  • Hartmann R
  • Jensen UB
  • Dagnaes-Hansen F
  • Thomsen AR
  • Chen Z
  • Haugen H
  • Klucher K
  • Paludan SR


Journal of immunology (Baltimore, Md. : 1950)

Publication Data

February 15, 2008

Associated Grants


Mesh Terms

  • Animals
  • Antiviral Agents
  • Crosses, Genetic
  • Cytokines
  • Epithelial Cells
  • Female
  • Hematopoietic Stem Cells
  • Herpes Genitalis
  • Herpesvirus 2, Human
  • Ligands
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Mutant Strains
  • Radiation Chimera
  • Receptors, Cytokine
  • Toll-Like Receptors