Review

Toll-like receptor downstream signaling

Taro Kawai¹ and Shizuo Akira^1,2*

• * Corresponding author: Shizuo Akira sakira@biken.osaka-u.ac.jp

Author Affiliations

¹ ERATO, Japan Science and Technology Agency, Osaka, Japan

² Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan

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Arthritis Res Ther 2005, 7:12-19 doi:10.1186/ar1469

Published: 30 November 2004

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.