Toll-like receptor downstream signaling 英文参考文献.docVIP

Arthritis Research Therapy Vol 7 No 1 Kawai and Akira Review Toll-like receptor downstream signaling Taro Kawai1 and Shizuo Akira1,2 1ERATO, Japan Science and Technology Agency, Osaka, Japan 2Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan Corresponding author: Shizuo Akira, sakira@biken.osaka-u.ac.jp Published: 30 November 2004 Arthritis Res Ther 2005, 7:12-19 (DOI 10.1186/ar1469) ? 2004 BioMed Central Ltd Abstract The 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-κB 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-β. Taken together, these results indicate that the interaction between individual TLRs and the different combinations of adapters directs appropriate responses against distinct pathogens. Keywords: inflammatory cytokines, innate immunity, interferons, TIR-domain containing adapter, TLR Introduction major domains characterized by leucine-rich repeats (LRR domain) and Toll/interleukin-1 receptor (TIR domain) domain (Fig. 1). The first evidence of TLRs in the recognition of pathogens was reported from studies with mice carrying a point-mutated or disrupted Tlr4 gene In Drosophila, Toll was initially identified as