Differential Requirement for TANK-binding Kinase-1 in Type I Interferon Responses to Toll-like Receptor Activation and Viral Infection
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- Andrea K. Perry
- 1Department of Microbiology, Immunology, and Molecular Genetics,
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- Edward K. Chow
- 2Molecular Biology Institute, and
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- Julia B. Goodnough
- 1Department of Microbiology, Immunology, and Molecular Genetics,
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- Wen-Chen Yeh
- 4Advanced Medical Discovery Institute,
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- Genhong Cheng
- 1Department of Microbiology, Immunology, and Molecular Genetics,
抄録
<jats:p>TANK-binding kinase-1 (TBK1) and the inducible IκB kinase (IKK-i) have been shown recently to activate interferon (IFN) regulatory factor-3 (IRF3), the primary transcription factor regulating induction of type I IFNs. Here, we have compared the role and specificity of TBK1 in the type I IFN response to lipopolysaccharide (LPS), polyI:C, and viral challenge by examining IRF3 nuclear translocation, signal transducer and activator of transcription 1 phosphorylation, and induction of IFN-regulated genes. The LPS and polyI:C-induced IFN responses were abolished and delayed, respectively, in macrophages from mice with a targeted disruption of the TBK1 gene. When challenged with Sendai virus, the IFN response was normal in TBK1−/− macrophages, but defective in TBK1−/− embryonic fibroblasts. Although both TBK1 and IKK-i are expressed in macrophages, only TBK1 but not IKK-i was detected in embryonic fibroblasts by Northern blotting analysis. Furthermore, the IFN response in TBK1−/− embryonic fibroblasts can be restored by reconstitution with wild-type IKK-i but not a mutant IKK-i lacking kinase activity. Thus, our studies suggest that TBK1 plays an important role in the Toll-like receptor–mediated IFN response and is redundant with IKK-i in the response of certain cell types to viral infection.</jats:p>
収録刊行物
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- The Journal of Experimental Medicine
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The Journal of Experimental Medicine 199 (12), 1651-1658, 2004-06-21
Rockefeller University Press
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詳細情報 詳細情報について
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- CRID
- 1360292619054622592
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- NII論文ID
- 30017421034
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- ISSN
- 15409538
- 00221007
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- データソース種別
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