Toll-like receptors: a growing family of immune receptors that are differentially expressed and regulated by different leukocytes

Toll is a Drosophila gene essential for ontogenesis and antimicrobial resis tance. Several hortologues of Toll hare been identified and cloned in verte brates, namely Toll-like receptors (TLR), Human TLR are a growing family of molecules involved in innate immunity. TLR are structurally characterized by a cytoplasmic Toll/interleukin-1R (TIR) domain and by extracellular leuc ine-rich repeats. TLR characterized so far activate the MyD88/IRAK signalin g cascade, which bifurcates and leads to KF-kappa B and c-Jun/ATF2/TCF acti vation, Genetic, gene transfer, and dominant-negative approaches ha ve invo lved TLR family members (TLR2 and TLR4) in lipopolysaccharide recognition a nd signaling. Accumulating evidence suggests that some TLR molecules are al so involved in signaling receptor complexes that recognize components of gr am-positive bacteria and mycobacteria, However, the definitive role of othe r TLR is still lacking, A systematic approach has been used to determine wh ether different human leukocyte populations selectively or specifically exp ressed TLR mRNA. Based on expression pattern, TLR can be classified as ubiq uitous (TLR1), restricted (TLR2, TLR4, and TLR5), and specific (TLR3), Expr ession and regulation of distinct though overlapping Ligand recognition pat terns may underlie the existence of a numerous, seemingly redundant, TLR fa mily. Alternately, the expression of a TLR in a single cell type mar indica te a specific role for this molecule in a restricted setting.