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Description
The Toll-Like Receptors (TLRs) represent a family of germline-encoded proteins, composed of C-terminal leucine-rich repeats (LRRs), and an N-terminal Toll/Interleukin-1 Receptor (TIR) domain. In humans, 10 TLRs, sharing high sequence homology, have been identified. TLRs are critical for the detection of pathogen-associated molecular patterns (PAMPs) by the innate immune system. LRRs recognize PAMPs, and signal transduction events, initiated by the TIR domain, lead to activation of transcription factors such as AP-1, IRFs and NFkB, and therefore expression of proinflammatory cytokines and costimulatory molecules. TLR7, TLR8 and TLR9 form a subgroup in the TLR family, because of a strong sequence homology and the nature of their ligands, which are nucleic acids or related molecules. TLR7 and TLR8 are triggered by GU-rich, single-stranded RNA (ssRNA) derived from viruses, or by synthetic small molecules mimicking ssRNA, such as imidazoquinolines. While TLR7 is expressed in lung, placenta and spleen, TLR8 expression is restricted to lung and peripheral blood leukocytes (PBLs). Heil F. et al,2003 ,Eur.J.Immunol, 33, 2987)