IRF-3, IRF-5, and IRF-7 Coordinately Regulate the Type I IFN Response in Myeloid Dendritic Cells Downstream of MAVS Signaling (original) (raw)
Figure 8
Model of Type I IFN and ISG induction in mDC.
WNV infection is sensed by PRR from the RLR family (RIG-I and MDA5, green) or TLR family (TLR3 and TLR7, yellow and orange). PRR signal through their respective adaptor molecules (MAVS, TRIF, MyD88), which activates cellular kinases (TBK1, IKKε, TRAF6, IRAK1). Phosphorylation of IRF-3, IRF-5, and IRF-7 (blue) induces nuclear localization, and in concert with other transcription factors (e.g., NF-κB), results in induced expression of Ifnb and ISGs. IRF-3, IRF-5, and IRF-7 are each sufficient to induce expression of IFN-β (red), which can signal through IFNAR to activate expression of hundreds of ISGs (pink). Some ISGs, including Ifna, Oas1a, and Pkr, are dependent strictly upon IFN signaling for their induction. Others, including Ifit1, Ifit2, Rsad2, and Cxcl10, can be induced directly by IRF-3, although IRF-5 apparently is not sufficient to induce these genes independently of IFN signaling. In addition to being activated by TLR7 signaling through MyD88, IRF-5 is activated by MAVS through an uncharacterized pathway.