Microbial recognition by Toll-like receptors.

Toll-like receptors (TLRs) sense invasion of microorganisms by detecting microbial components that are conserved among pathogens. Recognition of microbial components by TLRs triggers activation of the innate immune system. Signaling pathways via TLRs originate from conserved cytoplasmic Toll/IL-1 receptor (TIR) domains. Recent accumulating evidence demonstrates that TIR domain-containing adaptors, such as MyD88, TIRAP/Mal, TRIF, and TRAM, regulate TLR-mediated signaling pathways. MyD88 is common to all TLR-mediated pathways, which lead to the production of inflammatory cytokines, whereas TRIF mediates induction of IFN-beta in TLR3 and TLR4 signaling pathways. TIRAP/Mal is implicated in the TLR2- and TLR4-mediated MyD88-dependent signaling pathway. TRAM is specifically involved in the TLR4-mediated TRIF-dependent pathway. Thus, TIR domain-containing adaptors play a pivotal role in TLR signaling pathways, which culminate in pathogen-specific immune responses.