Fig. 2

Toll-like receptors 7/8 mediated downstream signaling pathways. TLRs located on the cell surface or endosome signal through MyD88-independent pathways or MyD88-dependent pathways. Upon activation of TLR7/8 ligands by TLRs in the endosomes, MyD88 binds to the cytoplasmic portion of TLRs through interaction between individual TIR domains. Receptor dimerization leads to downstream signaling, eventually leading to nuclear localization of transcription factors for pro-inflammatory factors. After TLR ligands stimulation, IRAK-4, IRAK-1, IRAK-2, IRAK-3, and TRAF6 are recruited to the receptor, which induces association of IRAK-1 and MyD88 via the death domains. IRAK-4 then phosphorylates IRAK-1. Phosphorylated IRAK-1 induces the activation phosphorylation of the IKK complex, consisting of IKKα, IKKβ, and NEMO/IKKγ, and IRF3/7, and thereby induces the activation of the transcription factors NF-κB and IRF3/7, respectively, which induce the secretion of different inflammatory cytokines, such as TNFα, IL12p40, IFNα, and IFNγ. Abbreviations: MyD88 (myeloid differentiation factor 88), IRAK (IL-1 receptor-associated kinase), IRF (interferon regulatory factor), TRAF (tumor necrosis factor receptor-associated factor), NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells)