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lüll Toll-like receptor downstream signaling Kawai T; Akira SArthritis Res Ther 2005[]; 7 (1): 12-9The family of Toll-like receptors (TLRs) senses conserved structures found in a broad range of pathogens, causing innate immune responses that include the production of inflammatory cytokines, chemokines and interferons. The signal transduction is initiated from the Toll/interleukin-1 receptor (TIR) domain of TLRs after pathogen recognition. Almost all TLRs use a TIR-containing adapter MyD88 to activate a common signaling pathway that results in the activation of NF-kappaB to express cytokine genes relevant to inflammation. Recently, three further TIR-containing adapters have been identified and shown to selectively interact with several TLRs. In particular, activation of the TRIF-dependent pathway confers antiviral responses by inducing anti-viral genes including that encoding interferon-beta. Taken together, these results indicate that the interaction between individual TLRs and the different combinations of adapters directs appropriate responses against distinct pathogens.|*Signal Transduction[MESH]|Adaptor Proteins, Signal Transducing/physiology[MESH]|Animals[MESH]|Arthritis, Rheumatoid/immunology/metabolism[MESH]|Drosophila Proteins/physiology[MESH]|Gene Expression Regulation[MESH]|Humans[MESH]|I-kappa B Kinase/physiology[MESH]|Infections/genetics/immunology/metabolism[MESH]|Inflammation/genetics/immunology/metabolism[MESH]|Ligands[MESH]|Mice[MESH]|Mice, Knockout[MESH]|Myeloid Differentiation Factor 88[MESH]|Protein Structure, Tertiary[MESH]|Receptors, Interleukin-1/physiology[MESH]|Toll-Like Receptors/chemistry/*physiology[MESH] |