Toll-like receptors (TLRs) play a critical role in the detection of invading pathogens within the body and the subsequent immune response. Individual TLRs recognize distinct microbial components. The TLRs are a type 1 transmembrane receptor that possess an extracellular leucine-rich repeat domain and cytoplasmic domain homologous with that of the interleukin 1 receptor (IL-1R) family. Upon stimulation, TLR recruits the IL-1R-associated kinase (IRAK) via the adapter MyD88, ultimately leading to the activation of nuclear factor-κB. Cytokine production in response to all TLR ligands is completely abolished in MyD88-deficient cells, indicating that MyD88 is an essential signalling molecule shared among members of the IL-1R/Toll family. However, several novel adaptor molecules have recently been identified. Evidence is now accumulating showing that differential utilization of these adaptors may activate overlapping as well as distinct signalling pathways, and ultimately give rise to distinct biological effects exerted by individual TLR family members.
Abbreviations used: TLR, Toll-like receptor; IL-1(R), interleukin-1 (receptor); IRAK, IL-1 receptor-associated kinase; TRAF, tumour-necrosis-factor-receptor-associated factor; NF-κB, nuclear factor κB; MAP, mitogen-activated protein; LPS, lipopolysaccharide; MALP-2, 2-kDa macrophage-activating lipopeptide; CpG, 2-deoxyribo(cytidine-phosphate-guanosine); ds, double-stranded; IFN, interferon; GARG16, glucocorticoid attenuated response gene 16; IRF-3, IFN regulatory factor 3; TIR, Toll/IL-1 receptor; TIRAP, TIR domain-containing adapter protein; Mal, MyD88-adaptor-like; Trif, TIR domain-containing adapter inducing IFNs.
Toll-Like Receptors, a Biochemical Society Focused Meeting held at Novartis, Horsham, 3 February 2003