Recognition and Signaling by Toll-Like Receptors

Toll-like receptors (TLRs) are transmembrane proteins that detect invading pathogens by binding conserved, microbially derived molecules and that induce signaling cascades for proinflammatory gene expression. A critical component of the innate immune system, TLRs utilize leucine-rich-repeat motifs for ligand binding and a shared cytoplasmic domain to recruit the adaptors MyD88, TRIF, TIRAP, and/or TRAM for downstream signaling. Despite significant domain conservation, TLRs induce gene programs that lead not only to the robust production of general proinflammatory mediators but also to the production of unique effectors, which provide pathogen-tailored immune responses. Here we review the mechanisms by which TLRs recognize pathogens and induce distinct signaling cascades.