| First Author | Ank N | Year | 2008 |
| Journal | J Immunol | Volume | 180 |
| Issue | 4 | Pages | 2474-85 |
| PubMed ID | 18250457 | Mgi Jnum | J:131989 |
| Mgi Id | MGI:3774908 | Doi | 10.4049/jimmunol.180.4.2474 |
| Citation | Ank N, et al. (2008) An important role for type III Interferon (IFN-lambda/IL-28) in TLR-induced antiviral activity. J Immunol 180(4):2474-85 |
| abstractText | 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. |
