Immune response Toll-like receptor (TLR) ligands and common TLR signaling pathway leading to cell proinflammatory response
Toll-like receptor (TLR) ligands and common TLR signaling pathway leadingto cell proinflammatory response Both gram-positive and gram-negative bacteria and their cell wall components activateinnate immune system of the host and induce secretion of proinflammatory molecules,mainly chemokines and cytokines . Toll-like receptors (TLRs) initiatesignaling cascades through recognition of a variety of microbial components, thus servingas an important link between innate and adaptive immune responses. Each TLR recognizesdistinct ligands . TLR2 agonists include peptidoglycan,lipoproteins, and lipopeptides from Gram-positive bacteria, mycobacteriallipoarabinomannan, mycoplasma lipopeptides , but only when present as aheterodimer in combination with either TLR1 or TLR6 .TLR3 and TLR5 mediate cell activation by double-stranded viral RNA andbacterial flagellin, respectively . TLR9 responds to unmethylatedCpG motif in bacterial DNA , . TLR4 is essentialin the respective recognition of lipopolysaccharide ( LPS ) ,lipoteichoic acid  and some other substrates , , . A number of microbial substrates are known for TLR7and TLR8 , ,. The main TLR-mediated immune response pathway, which is common for all TLRs, isMyeloid differentiation primary response gene 88 ( MyD88 )-dependent activation ofNuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor (NF-kB ) and c-Jun, transcription regulators of number of chemokines andcytokines responsible for cellular immune response. The main steps of NF-kBactivation involve MyD88/ Interleukin-1 receptor-associated kinases ( IRAK)/ TNF receptor-associated factor 6 ( TRAF6 )/ Mitogen-activated protein kinasekinase kinase 14 ( NIK )/ Inhibitor of kappa light polypeptide gene enhancer inB-cells ( IKK )/ NF-kB signal transduction . C-Junactivation proceeds throw MyD88/ IRAK/ TRAF6/ Mitogen-activatedprotein kinase kinase kinase 7 interacting protein 1 ( TAB )/ Mitogen-activatedprotein kinase kinase kinase 7 ( TAK ) cascade , .Besides MyD88, some TLR s use alternative adaptor proteins to induceNF-kB and c-Jun activation, such as Toll-interleukin 1 receptor domaincontaining adaptor protein ( TIRAP ) , . Certaintypes of TLRs (for example, TLR3 and TLR4 ) demonstrate also other responsepathways, which are specific for them.