Toll-like receptor family: receptors essential for microbial recognition and immune responses

Toll-like receptors (TLRs) play a critical role in the detection of invading pathogens within the body and subsequent immune response against them. We have generated knockout mice for individual TLRs and showed that individual TLRs recognize distinct microbial components. TLR4 is essential for the response to LPS. TLR2 is involved in the recognition of lipoproteins and peptidoglycan, together with TLR1 or TLR6. TLR9, TLR3, TLR5 and TLR7 recognize deoxyribonucleotides, ribonucleotides, flagellin, and imidazoquinolines, respectively. The TLR is a type 1 transmembrane receptor that is composed of an extracellular leucine-rich repeat domain and a cytoplasmic domain homologous to that of the IL-1R family. Upon stimulation, TLR recruits IL-1 receptor-associated kinase via adaptor MyD88, and finally induces activation of NF-κB. Cytokine production in response to each TLR ligand is completely abolished in MyD88-deficient cells, indicating that MyD88 is an essential signaling molecule shared among the IL-1R/Toll family. However, several novel adaptor molecules have recently been identified. Evidence is now accumulating that differential utilization of these adaptors may activate overlapping as well as distinct signaling pathways, and finally may give rise to distinct biological effects exerted by individual TLR families.