Differential involvement of adaptor molecules in individual TLR signalings*1

Innate immune response is a first-line defense system in which individual Toll-like receptors recognize distinct pathogen-associated molecular patterns (PAMPs) and exert subsequent immune responses against a variety of pathogens. TLRs are composed of an extracellular leucine-rich repeat (LRR) domain and a cytoplasmic domain that is homologous to that of the IL-1R family. Upon stimulation, TLR recruits IRAK via adaptor MyD88, and finally induces activation of NF-κB and MAP kinases. However, the response to TLR ligands differs each other, indicating the diversity of TLR signaling pathways. Besides MyD88, several novel adaptor molecules have recently been identified. Differential utilization of these adaptor molecules may provide the specificity in the TLR signaling.