Immune response Role of TLRs 3 and 4 in cell antiviral response: TICAM1-specific signaling pathways
Role of TLRs 3 and 4 in cell antiviral response: TICAM1-specific signalingpathways Toll-like receptors ( TLR ) initiate signaling cascades through recognition ofa variety of microbial components, thus serving as an important link between innate andadaptive immune responses. Each TLR recognizes distinct ligands by means of itsleucine-rich repeats and elicits different, but often overlapping immune responses . TLR3 -induced signaling pathways are triggered by binding of virus-deriveddouble-stranded RNA , whereas TLR4 becomes activated after bindingto number of bacterial cell wall components: Lipopolysaccharide ( LPS ) , Pulmonary surfactant-associated protein A ( PSAP ) ,Paclitaxel , Fibronectin ,Pneumolysin . Although Myeloid differentiation primary response gene 88 ( MyD88 )-dependentsignaling pathway is common for all TLR s, TLR3 - and TLR4 -inducedactivation of the transcription factor nuclear factor kappa B ( NF-kB ) can bemediated by some alternative adaptors. It can be activated by TLR3 ligands viaToll-like receptor adaptor molecule 1 ( TRIF (TICAM1) ) .TLR4 signaling can also be mediated by TRIF (TICAM1), which binds toTLR4 adaptor Toll-like receptor adaptor molecule 2 ( TRAM ) . TLR4 activates NF-kB independently of TRIF (TICAM1)through its other adaptor, Toll-interleukin 1 receptor domain containing adaptor protein( TIRAP (Mal) ) . TRIF (TICAM1) -dependent NF-kBactivation is mediated either by TNF receptor-associated factor 6 ( TRAF6 ) or byReceptor TNFRSF-interacting serine-threonine kinase 1 ( RIPK1 )-induced kinasecascade . Moreover, TRIF (TICAM1) causes activation oftranscription factor Interferon regulatory factor 3 ( IRF3 ) .Both IRF3 and NF-kB regulate expression of such proinflammatory moleculesas Interferon alpha and beta ( IFN-alpha and IFN-beta ), thus mediating theantiviral action of interferon.