Both TLR2 and TRIF contribute to interferon-β production during Listeria infection
Résumé
Synthesis of interferon-beta (IFN-beta) is an innate response to cytoplasmic infection with bacterial pathogens. Our recent studies showed that Listeria monocytogenes limits immune detection and IFN-beta synthesis via deacetylation of its peptidoglycan, which renders the bacterium resistant to lysozyme degradation. Here, we examined signaling requirements for the massive IFN-beta production resulting from the infection of murine macrophages with a mutant strain of L. monocytogenes, Delta pgdA, which is unable to modify its peptidoglycan. We report the identification of unconventional signaling pathways to the IFN-beta gene, requiring TLR2 and bacterial internalization. Induction of IFN-beta was independent of the Mal/TIRAP adaptor protein but required TRIF and the transcription factors IRF3 and IRF7. These pathways were stimulated to a lesser degree by wild-type L. monocytogenes. They operated in both resident and inflammatory macrophages derived from the peritoneal cavity, but not in bone marrow-derived macrophages. The novelty of our findings thus lies in the first description of TLR2 and TRIF as two critical components leading to the induction of the IFN-beta gene and in uncovering that individual macrophage populations adopt different strategies to link pathogen recognition signals to IFN-beta gene expression.
Domaines
Sciences du Vivant [q-bio]Origine | Fichiers éditeurs autorisés sur une archive ouverte |
---|
Loading...