TICAM-1, an adaptor molecule that participates in Toll-like receptor 3–mediated interferon-β induction

Abstract

Human Toll-like receptor (TLR) 3 recognizes double-stranded (ds) RNA and induces production of interferon (IFN)-β independent of the adaptor molecules MyD88 and TIRAP. Thus, another adaptor must exist that preferentially mediates TLR3-dependent production of IFN-β. We have identified an alternative adaptor, designated Toll-interleukin 1 receptor domain (TIR)-containing adaptor molecule (TICAM)-1, that can physically bind the TIR domain of TLR3 and activate the IFN-β promoter in response to poly(I):poly(C). Thus, dsRNA-TLR3–dependent production of IFN-β is mediated mainly by TICAM-1. This TICAM-1–dependent pathway may have a role in other TLR–IFN-β pathways, which form part of the MyD88-independent cellular immune response.

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Figure 1: TLR3-mediated IFN-β activation is MyD88- and TIRAP-independent.
Figure 2: Molecular cloning and distribution of TICAM-1.
Figure 3: TICAM-1 associates with TLR3.
Figure 4: TICAM-1 overexpression activates NF-κB and IFN-β promoters.
Figure 5: TICAM-1 activates AP-1 and IRF-3.
Figure 6: TICAM-1–mediated signaling links to production of IFN-β.

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Acknowledgements

We thank D.T. Fearon, Y. Murakami and N. Inoue for critical reading of the manuscript; T. Taniguchi and T. Fujita for providing p-125 luc reporter plasmid and anti–IRF-3 Ab, respectively; and S. Akira and K. Miyake for providing MyD88−/− mice and an expression vector for MD-2. This work was supported in part by Grants-in-Aid from the Ministry of Education, Science, and Culture (Scientific Research on Priority Areas), and the Ministry of Health and Welfare, of Japan.

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Correspondence to Tsukasa Seya.

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Oshiumi, H., Matsumoto, M., Funami, K. et al. TICAM-1, an adaptor molecule that participates in Toll-like receptor 3–mediated interferon-β induction. Nat Immunol 4, 161–167 (2003). https://doi.org/10.1038/ni886

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