Fig. 3

Toll-like receptor (TLR) signaling pathways and involved effector molecules. TLR 1, 2, 4, 5, and 6 are in homodimer or heterodimer forms are located on the cell surfaces, when stimulated by PAMPs, MyD88 interacts with IRAK-4 MyD88-IRAK-4 complex, recruits IRAK-1 and IRAK-2, resulting in the phosphorylation of IRAKs. Phosphorylated IRAKs leave MyD88 after and interact with TRAF6. TRAF6 induces the activation of TAK-1 and TAB2/3 then activation of IκB and MAPK occurs. The activation of IκB and MAPK result in the subsequent translocation of AP1 and NFkB to nucleus. TLR3, 7, 8, and 9 are located on the endosomal membrane. Stimulation of endosomal TLRs leads to the recruitment of MyD88, IRAK4, IRAK1, and TRAF6 and the translocation of IRF7 to nucleusTLR3 and part of TLR4 use TRIF as their adaptor. The interaction of TRIF with RIP1 leads to RIP1 polyubiquitination and their combination with TAB2 and TAB3, result in the translocation of NF-κB and AP-1 nucleus. The nuclear translocation of transcription factors including the NFκB in early and late stages (all TLRs), AP-1 (all except TLR 3), the IRF-3 (TLR3 and TLR4) and IRF-7 (TLR7/8/9) occur. These pathways lead to inflammatory cytokine synthesis, secretion in the case of platelets and the production type 1 IFNs [84, 85]