title: Both TLR2 and TRIF contribute to interferon-β production during Listeria infection.
abstract: Synthesis of interferon-β (IFN-β) is an innate response to cytoplasmic infection with bacterial pathogens. Our recent studies showed that Listeria monocytogenes limits immune detection and IFN-β synthesis via deacetylation of its peptidoglycan, which renders the bacterium resistant to lysozyme degradation. Here, we examined signaling requirements for the massive IFN-β production resulting from the infection of murine macrophages with a mutant strain of L. monocytogenes, ΔpgdA, which is unable to modify its peptidoglycan. We report the identification of unconventional signaling pathways to the IFN-β gene, requiring TLR2 and bacterial internalization. Induction of IFN-β 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-β gene and in uncovering that individual macrophage populations adopt different strategies to link pathogen recognition signals to IFN-β gene expression.
authors.affiliation: Institut Pasteur, Unité des Interactions Bactéries-Cellules, Paris, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Aubry
authors.forename: Sinéad C
authors.initials: SC
authors.lastname: Corr
authors.forename: Sebastian
authors.initials: S
authors.lastname: Wienerroither
authors.forename: Céline
authors.initials: C
authors.lastname: Goulard
authors.forename: Ruth
authors.initials: R
authors.lastname: Jones
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Jamieson
authors.forename: Thomas
authors.initials: T
authors.lastname: Decker
authors.forename: Luke A J
authors.initials: LA
authors.lastname: O'Neill
authors.forename: Olivier
authors.initials: O
authors.lastname: Dussurget
authors.forename: Pascale
authors.initials: P
authors.lastname: Cossart
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism*; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D001854:Bone Marrow Cells / Q000473:pathology; D004705:Endocytosis; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D050839:Interferon Regulatory Factor-7 / Q000378:metabolism; D016899:Interferon-beta / Q000096:biosynthesis*; D042541:Intracellular Space / Q000378:metabolism / Q000382:microbiology; D008088:Listeriosis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D017737:Macrophages, Peritoneal / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism; D009696:Nucleic Acids / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D051196:Toll-Like Receptor 3 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D001426:Bacterial Proteins; D050838:Interferon Regulatory Factor-3; D050839:Interferon Regulatory Factor-7; D016899:Interferon-beta; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D009696:Nucleic Acids; D017472:Receptors, Interleukin-1; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; C494233:Irf3 protein, mouse; C494235:Irf7 protein, mouse; C476286:Ticam1 protein, mouse; C499045:TIRAP protein, mouse; C519703:TLR3 protein, mouse; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse