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CUTTING EDGE |
B Kinase in IFN Responses against Viruses in Innate Immune Cells1
* Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan; and
Exploratory Research for Advanced Technology, Japan Science and Technology Agency, Suita, Osaka, Japan
TANK-binding kinase 1 (TBK1) and inducible I
B 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-
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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported, in part, by grants from the Ministry of Education, Culture, Sports, Science, and Technology in Japan, and from the 21st Century Center of Excellence Program of Japan.
2 Address correspondence and reprint requests to Dr. Shizuo Akira, Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan. E-mail address: sakira{at}biken.osaka-u.ac.jp
3 Abbreviations used in this paper: RIG-I, retinoic acid-inducible protein-I; MDA5, melanoma differentiation-associated gene-5; CARD, comprised of caspase recruitment domain; VSV, vesicular stomatitis virus; EMCV, encephalomyocarditis virus; TRIF, TIR-domain-containing adaptor-inducing IFN-
; TBK1, TANK-binding kinase 1; IKK-i, inducible IB kinase; IRF, IFN-regulatory factor; pDC, plasmacytoid dendritic cell; cDC, conventional DC; NDV, Newcastle disease virus; Q-PCR, quantitative real-time PCR; moi, multiplicity of infection; IRAK, IL-1R-associated kinase; Flt3L, Fms-like tyrosine kinase 3 ligand.
4 The online version of this article contains supplemental material.
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