| First Author | Stockinger S | Year | 2004 |
| Journal | J Immunol | Volume | 173 |
| Issue | 12 | Pages | 7416-25 |
| PubMed ID | 15585867 | Mgi Jnum | J:94858 |
| Mgi Id | MGI:3521616 | Doi | 10.4049/jimmunol.173.12.7416 |
| Citation | Stockinger S, et al. (2004) IFN regulatory factor 3-dependent induction of type I IFNs by intracellular bacteria is mediated by a TLR- and Nod2-independent mechanism. J Immunol 173(12):7416-25 |
| abstractText | Like viruses, intracellular bacteria stimulate their host cells to produce type I IFNs (IFN-alpha and IFN-beta). In our study, we investigated the signals and molecules relevant for the synthesis of and response to IFN by mouse macrophages infected with Listeria monocytogenes. We report that IFN-beta is the critical immediate-early IFN made during infection, because the synthesis of all other type I IFN, expression of a subset of infection-induced genes, and the biological response to type I IFN was lost upon IFN-beta deficiency. The induction of IFN-beta mRNA and the IFN-beta-dependent sensitization of macrophages to bacteria-induced death, in turn, was absolutely dependent upon the presence of the transcription factor IFN regulatory factor 3 (IRF3). IFN-beta synthesis and signal transduction occurred in macrophages deficient for TLR or their adaptors MyD88, TRIF, or TRAM. Expression of Nod2, a candidate receptor for intracellular bacteria, increased during infection, but the protein was not required for Listeria-induced signal transduction to the Ifn-beta gene. Based on our data, we propose that IRF3 is a convergence point for signals derived from structurally unrelated intracellular pathogens, and that L. monocytogenes stimulates a novel TLR- and Nod2-independent pathway to target IRF3 and the type I IFN genes. |
