title: Cutting edge: Role of TANK-binding kinase 1 and inducible IkappaB kinase in IFN responses against viruses in innate immune cells.
abstract: TANK-binding kinase 1 (TBK1) and inducible IkappaB kinase (IKK-i) are involved in the activation of transcription factors inducing the production of type I IFNs. Although TBK1, but not IKK-i, is critical for LPS-induced IFN induction, the role of these kinases in the responses against viral infection is yet to be determined. In this study, we show that type I IFN production against various RNA viruses was completely abrogated in conventional dendritic cells (DCs) and macrophages induced from fetal liver cells lacking both TBK1 and IKK-i, whereas considerable amounts of IFN were produced in cells lacking either of them. Microarray analysis revealed that various IFN-inducible genes were also regulated by the kinases. In contrast, Fms-like tyrosine kinase 3 ligand-induced DCs produced IFN-alpha even in the absence of both TBK1 and IKK-i. Thus, these two kinases are essential and compensate each other for the regulation of IFN responses in innate immune cells except plasmacytoid DCs.
authors.affiliation: Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Matsui
authors.forename: Yutaro
authors.initials: Y
authors.lastname: Kumagai
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kato
authors.forename: Shintaro
authors.initials: S
authors.lastname: Sato
authors.forename: Tatsukata
authors.initials: T
authors.lastname: Kawagoe
authors.forename: Satoshi
authors.initials: S
authors.lastname: Uematsu
authors.forename: Osamu
authors.initials: O
authors.lastname: Takeuchi
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000201:enzymology / Q000276:immunology*; D005786:Gene Expression Regulation; D051550:I-kappa B Kinase / Q000235:genetics / Q000502:physiology*; D007113:Immunity, Innate / Q000235:genetics; D050838:Interferon Regulatory Factor-3 / Q000819:agonists; D007370:Interferon Type I / Q000378:metabolism*; D008024:Ligands; D051379:Mice; D008817:Mice, Mutant Strains; D009522:Newcastle disease virus / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D012328:RNA Viruses / Q000502:physiology*; D051941:fms-Like Tyrosine Kinase 3 / Q000494:pharmacology
chemical_list: D050838:Interferon Regulatory Factor-3; D007370:Interferon Type I; D008024:Ligands; C498588:Tbk1 protein, mouse; D051941:fms-Like Tyrosine Kinase 3; D017346:Protein Serine-Threonine Kinases; D051550:I-kappa B Kinase; C496566:Ikbke protein, mouse