title: Co-ordinated role of TLR3, RIG-I and MDA5 in the innate response to rhinovirus in bronchial epithelium.
abstract: The relative roles of the endosomal TLR3/7/8 versus the intracellular RNA helicases RIG-I and MDA5 in viral infection is much debated. We investigated the roles of each pattern recognition receptor in rhinovirus infection using primary bronchial epithelial cells. TLR3 was constitutively expressed; however, RIG-I and MDA5 were inducible by 8-12 h following rhinovirus infection. Bronchial epithelial tissue from normal volunteers challenged with rhinovirus in vivo exhibited low levels of RIG-I and MDA5 that were increased at day 4 post infection. Inhibition of TLR3, RIG-I and MDA5 by siRNA reduced innate cytokine mRNA, and increased rhinovirus replication. Inhibition of TLR3 and TRIF using siRNA reduced rhinovirus induced RNA helicases. Furthermore, IFNAR1 deficient mice exhibited RIG-I and MDA5 induction early during RV1B infection in an interferon independent manner. Hence anti-viral defense within bronchial epithelium requires co-ordinated recognition of rhinovirus infection, initially via TLR3/TRIF and later via inducible RNA helicases.
authors.affiliation: Department of Respiratory Medicine, National Heart & Lung Institute, Imperial College London, London, United Kingdom.
authors.forename: Louise
authors.initials: L
authors.lastname: Slater
authors.forename: Nathan W
authors.initials: NW
authors.lastname: Bartlett
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Haas
authors.forename: Jie
authors.initials: J
authors.lastname: Zhu
authors.forename: Simon D
authors.initials: SD
authors.lastname: Message
authors.forename: Ross P
authors.initials: RP
authors.lastname: Walton
authors.forename: Annemarie
authors.initials: A
authors.lastname: Sykes
authors.forename: Samer
authors.initials: S
authors.lastname: Dahdaleh
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Clarke
authors.forename: Maria G
authors.initials: MG
authors.lastname: Belvisi
authors.forename: Onn M
authors.initials: OM
authors.lastname: Kon
authors.forename: Takashi
authors.initials: T
authors.lastname: Fujita
authors.forename: Peter K
authors.initials: PK
authors.lastname: Jeffery
authors.forename: Sebastian L
authors.initials: SL
authors.lastname: Johnston
authors.forename: Michael R
authors.initials: MR
authors.lastname: Edwards
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001980:Bronchi / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D002478:Cells, Cultured; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004848:Epithelium / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D005260:Female; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells; D006801:Humans; D007113:Immunity, Innate; D000072640:Interferon-Induced Helicase, IFIH1; D051379:Mice; D018345:Mice, Knockout; D010850:Picornaviridae Infections / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D012330:RNA, Double-Stranded; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D053633:Receptor, Interferon alpha-beta / Q000502:physiology; D011971:Receptors, Immunologic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012229:Rhinovirus / Q000472:pathogenicity*; D051196:Toll-Like Receptor 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: C508032:Ifnar1 protein, mouse; D012330:RNA, Double-Stranded; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D012367:RNA, Viral; D011971:Receptors, Immunologic; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D053633:Receptor, Interferon alpha-beta; C452820:RIGI protein, human; C452815:IFIH1 protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1