title: Cross-interference of RLR and TLR signaling pathways modulates antibacterial T cell responses.
abstract: Although the mechanisms by which innate pathogen-recognition receptors enhance adaptive immune responses are increasingly well understood, whether signaling events from distinct classes of receptors affect each other in modulating adaptive immunity remains unclear. We found here that the activation of cytosolic RIG-I-like receptors (RLRs) resulted in the selective suppression of transcription of the gene encoding the p40 subunit of interleukin 12 (Il12b) that was effectively induced by the activation of Toll-like receptors (TLRs). The RLR-activated transcription factor IRF3 bound dominantly, relative to IRF5, to the Il12b promoter, where it interfered with the TLR-induced assembly of a productive transcription-factor complex. The activation of RLRs in mice attenuated TLR-induced responses of the T helper type 1 cell (T(H)1 cell) and interleukin 17-producing helper T cell (T(H)17 cell) subset types and, consequently, viral infection of mice caused death at sublethal doses of bacterial infection. The innate immune receptor cross-interference we describe may have implications for infection-associated clinical episodes.
authors.affiliation: Department of Molecular Immunology, Institute of Industrial Science, University of Tokyo, Tokyo, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Negishi
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Yanai
authors.forename: Akira
authors.initials: A
authors.lastname: Nakajima
authors.forename: Ryuji
authors.initials: R
authors.lastname: Koshiba
authors.forename: Koji
authors.initials: K
authors.lastname: Atarashi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Matsuda
authors.forename: Kosuke
authors.initials: K
authors.lastname: Matsuki
authors.forename: Shoji
authors.initials: S
authors.lastname: Miki
authors.forename: Takahiro
authors.initials: T
authors.lastname: Doi
authors.forename: Alan
authors.initials: A
authors.lastname: Aderem
authors.forename: Junko
authors.initials: J
authors.lastname: Nishio
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Smale
authors.forename: Kenya
authors.initials: K
authors.lastname: Honda
authors.forename: Tadatsugu
authors.initials: T
authors.lastname: Taniguchi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001424:Bacterial Infections / Q000276:immunology; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000276:immunology; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D050835:Interferon Regulatory Factors / Q000378:metabolism; D053762:Interleukin-12 Subunit p40 / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D051193:Toll-Like Receptors / Q000276:immunology*; D014157:Transcription Factors / Q000378:metabolism; D014777:Virus Diseases / Q000276:immunology
chemical_list: D050838:Interferon Regulatory Factor-3; D050835:Interferon Regulatory Factors; D053762:Interleukin-12 Subunit p40; C494233:Irf3 protein, mouse; C498178:Irf5 protein, mouse; D051193:Toll-Like Receptors; D014157:Transcription Factors