title: Double-stranded RNA of intestinal commensal but not pathogenic bacteria triggers production of protective interferon-β.
abstract: The small intestine harbors a substantial number of commensal bacteria and is sporadically invaded by pathogens, but the response to these microorganisms is fundamentally different. We identified a discriminatory sensor by using Toll-like receptor 3 (TLR3). Double-stranded RNA (dsRNA) of one major commensal species, lactic acid bacteria (LAB), triggered interferon-β (IFN-β) production, which protected mice from experimental colitis. The LAB-induced IFN-β response was diminished by dsRNA digestion and treatment with endosomal inhibitors. Pathogenic bacteria contained less dsRNA and induced much less IFN-β than LAB, and dsRNA was not involved in pathogen-induced IFN-β induction. These results identify TLR3 as a sensor to small intestinal commensal bacteria and suggest that dsRNA in commensal bacteria contributes to anti-inflammatory and protective immune responses.
authors.affiliation: Biomedical Research Institute, National Institute for Advanced Industrial Science and Technology-AIST, Tsukuba, Ibaraki 305-8566, Japan.
authors.forename: Tadaomi
authors.initials: T
authors.lastname: Kawashima
authors.forename: Akemi
authors.initials: A
authors.lastname: Kosaka
authors.forename: Huimin
authors.initials: H
authors.lastname: Yan
authors.forename: Zijin
authors.initials: Z
authors.lastname: Guo
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Uchiyama
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Fukui
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kaneko
authors.forename: Yutaro
authors.initials: Y
authors.lastname: Kumagai
authors.forename: Dong-Ju
authors.initials: DJ
authors.lastname: You
authors.forename: Joaquim
authors.initials: J
authors.lastname: Carreras
authors.forename: Satoshi
authors.initials: S
authors.lastname: Uematsu
authors.forename: Myoung Ho
authors.initials: MH
authors.lastname: Jang
authors.forename: Osamu
authors.initials: O
authors.lastname: Takeuchi
authors.forename: Tsuneyasu
authors.initials: T
authors.lastname: Kaisho
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Kensuke
authors.initials: K
authors.lastname: Miyake
authors.forename: Hiroko
authors.initials: H
authors.lastname: Tsutsui
authors.forename: Takashi
authors.initials: T
authors.lastname: Saito
authors.forename: Ikuko
authors.initials: I
authors.lastname: Nishimura
authors.forename: Noriko M
authors.initials: NM
authors.lastname: Tsuji
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003092:Colitis / Q000209:etiology / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D004195:Disease Models, Animal; D056569:Enterococcaceae / Q000276:immunology* / Q000472:pathogenicity; D005260:Female; D016908:Gram-Positive Bacterial Infections / Q000150:complications / Q000276:immunology* / Q000382:microbiology; D016899:Interferon-beta / Q000378:metabolism*; D007422:Intestines / Q000276:immunology / Q000382:microbiology; D007778:Lactobacillus / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D026901:Membrane Transport Proteins / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D012330:RNA, Double-Stranded / Q000276:immunology; D051196:Toll-Like Receptor 3 / Q000378:metabolism*
chemical_list: D026901:Membrane Transport Proteins; D012330:RNA, Double-Stranded; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; C512254:UNC93B1 protein, mouse; D016899:Interferon-beta