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Fig. 4 | Journal of Hematology & Oncology

Fig. 4

From: Toll-like receptors and toll-like receptor-targeted immunotherapy against glioma

Fig. 4

The TLR signaling pathways. TLRs are located on either plasma membrane or endosomal membranes where they detect PAMPs or DAMPs. TLRs trigger two main pathways: the MyD88-dependent and MyD88-independent pathways. The MyD88-dependent pathway is initiated after surface (TLR1/2, TLR2/6, TLR4, and TLR5) or intracellular TLRs (TLR7, TLR8, and TLR9) binding to corresponding ligands. Recruitment of MyD88 to the TIR domain of TLRs induces myddosome formation which involves MyD88, IRAK, and TRAF6. IRAK and TRAF6 stimulate TAK1 to activate IKKγ complex, which further releases NF-κB into the nucleus. The activated TAK1 also promotes MAPK activation which in turn stimulates AP-1 nucleus translocation. Both routes support proinflammatory cytokine transcription. In parallel, the myddosome also initiates IRF5 and IRF7 production to induce type I IFN gene expression. The MyD88-independent pathway is activated by TLR3 and TLR4. The TIR domain of TLRs recruits TRIF to form a complex containing TRAF3, TBK1, and IKK, which promotes nucleus translocation of IRF3, or initiation of a late phase NF-κB via interaction with RIP1 and subsequent TRAF6 activation. Both signaling stimulates the production of type I IFNs. The detailed signaling pathway is described in the text

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