Cutting edge:: Role of TANK-binding kinase 1 and inducible IκB kinase in IFN responses against viruses in innate inunune cells

TANK-binding kinase 1 (TBK1) and inducible I kappa B kinase (HiX-i) are involved in the activation of transcription factors inducing the production of type I IFNs. Although TBK1, but not IAK-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 IIFN production against various RNA viruses was completely abrogated in conventional dendritic cells (DCs) and macrophages induced from fetal liver cells lacking both TBK1 and IKX-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 DO.