An important role for type III interferon (IFN-lambda/IL-28) in TLR-induced antiviral activity
Research output: Contribution to journal › Journal article › Research › peer-review
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.
Original language | English |
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Journal | Journal of Immunology |
Volume | 180 |
Issue number | 4 |
Pages (from-to) | 2474-85 |
Number of pages | 11 |
ISSN | 0022-1767 |
Publication status | Published - 2008 |
Bibliographical note
Keywords: 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
ID: 9701135