Toll-like receptor family and signalling pathway

Toll is a Drosophila gene essential for ontogenesis and anti-microbial resi stance. Several orthologues of Toll have been identified and cloned in vert ebrates, namely Toll-like receptors (TLRs). Human TLRs are a growing family of molecules involved in innate immunity. TLRs are characterized structura lly by a cytoplasmic Toll/interleukin-1 receptor (TIR) domain and by extrac ellular leucine-rich repeats. TLRs characterized so far activate the MyD88/ interleukin-1 receptor-associated kinase (IRAK() signalling pathway. Geneti c, gene-transfer and dominant-negative approaches have involved TLR family members (TLR2 and TLR4) in Gram-positive and Gramnegative bacteria recognit ion and signalling. Accumulating evidence suggests that TLR2 is also involv ed in signalling-receptor complexes that recognize components of yeast and mycobacteria. However, the definitive roles of other TLRs are still lacking . A systematic approach has been used to determine whether different human leucocyte populations selectively or specifically express TLR mRNA. Based o n expression pattern, TLR can be classified as ubiquitous (TLR1), restricte d (TLR2, TLR4 and TLR5) and specific (TLR3). Expression and regulation of d istinct but overlapping ligand-recognition patterns may underlie the existe nce of a large, seemingly redundant TLR family. Alternatively, the expressi on of a TLR in a single cell type may indicate a specific role for this mol ecule in a restricted setting.