Fig. 1

By attaching to their ligands and experiencing conformational changes, all TLRs except for TLR3 recruit the MyD88 adaptive molecule. MyD88 then activates and recruits IRAK1, IRAK2, and IRAK4, forming a complex named Myddosome. Myddosome then recruits and activates TRAF6, followed by activation of TAK1. The activation of TAK1 resulted in the activation and transfer of different transcription factors, including NF-kB, JNK, and AP1, leading to proinflammatory cytokine production. Moreover, TRAF6 can activate IRF7 leading to interferons production. On the other side, TLR3 utilizes the TRIF adaptive molecule, which by activating TRAF3 and TBK leads to activation and transfer of IRF3 to the nucleus and interferons production. Moreover, TRIF can activate TRAF6 and result in MyD88-independent proinflammatory cytokine production. Furthermore, TLR4 can use both MyD88 and TRIF adaptor proteins. It should be mentioned that some TLRs like TLR4 can use coreceptors like CD14 and MD2 for attaching more efficiently to their ligands. Myddosome can be inhibited by several factors, including FADD, TOLLIP, IRAK-M, and SHIP-1. For instance, FADD can antagonize MyD88 or IRAK molecules and their interaction, IRAK-M can inhibit IRAK1 molecule, and TOLLIP can inhibit IRAK phosphorylation and kinase activity [33, 34]. Other examples of TLR regulators are SH2-containing inositol-5′-phosphatase (SHIP) 1 and SHIP2, which contribute to dephosphorylation and inactivation of IRAK1 and TBK1. TLR toll-like receptor, LPS lipopolysaccharide, CD14 cluster of differentiation 14, MD2 Myeloid Differentiation factor 2, MyD88 Myeloid differentiation primary response 88, IRAK4 Interleukin-1 receptor-associated kinase, TRAF6 TNF (tumor necrosis factor) receptor-associated factor 6, TAK1 transforming growth factor b-activated kinase 1, MKK mitogen-activated protein kinase kinase, JNK Jun N-terminal Kinase, IRF Interferon regulatory factor, P38MAPK P38 mitogen-activated protein kinase, AP1 Activating Protein-1, NF-kB nuclear factor kappa-light-chain-enhancer of activated B cells, TRIF TIR-domain-containing adaptor-inducing interferon-β, LBP Lipopolysaccharide binding protein, TIR Toll/interleukin-1 receptor, TANK binding kinase 1, FADD Fas-associated protein with death domain, TOLLIP toll interacting protein, SHIP SH2-containing inositol-5′-phosphatase, dsRNA double-stranded RNA, ssRNA single-stranded RNA