Fig. 1.

The signaling pathways for TLRs. Cell membrane receptors, TLR2/1, TLR2/6, TLR5 and TLR4, and endosomal membrane receptors, TLR7, TLR8 and TLR9 are activated by their ligands. Then they interact with MyD88 and recruit the IRAK complex and TRAF6 to activate TAK1. TAK1 not only activates IKK complex to induce NF-κB activation, but also activates MKK to induce AP1 activation, which result in the transcription of proinflammatory cytokines (IL-1β, IL-6, IL-8 and TNF-α). Activation of TLR7, TlR8 and TLR9 trigger the IRAK-TRAF6-TRAF3-IKKα-dependent activation of IRF7, leading to transcription of type I IFNs. TLR3 signals not only through TRIF-TRAF6-RIP1-TAK1-dependent activation of NF-κB and AP1 pathways, but also through TBK1 dependent activation of IRF3 pathway. TLR4 initially signals on cell membrane through MyD88-dependent pathway. Subsequently, receptor internalization into endosomes triggers TRIF-dependent pathway, but additionally requires TRAM. The ligand and signaling pathway of TLR10 remain unclear