Figure 1: TLR3-TRIF mediated pathway. TLR3 is the only TLR that exclusively signals through the TRIF-dependent pathway. The association of TLR3/TRIF TIR domains activates TRAF3 and the downstream signaling events, represented by IKK/NF-κB pathway, that in turn is regulated by Peli 1. Peli 1, activated by TBK1 and IKKε, induces the IRF3 phosphorylation, dimerization and translocation to the nucleus, so leading to IFNβ gene transcription. IFNβ stimulates the JAK/STAT pathway, that induces the STAT1 and STAT2 phosphorylation, and the association of STAT1/2 with IRF9. This multimeric regulator stimulates IRF7, that in turn activates the IFNβ promoter either directly, or as IRF3/IRF7 heterodimer [67].