Toll-like receptor signaling

doi:10.1017/CBO9780511541551.003

2 - Toll-like receptor signaling

from I - Dendritic cells and their role in immunity

Published online by Cambridge University Press: 12 August 2009

Osamu Takeuchi and

Shizuo Akira

Edited by

Maria Rescigno

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Maria Rescigno: Affiliation:
European Institute of Oncology, Milan

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Summary

INTRODUCTION

Toll-like receptors (TLRs) play essential roles in innate immune responses. The name TLR is derived from a Drosophila protein, Toll, which detects fungal infection in the fruit fly. The immune system in Drosophila is entirely dependent on a limited number of germline-encoded receptors for pathogen recognition. In contrast, the vertebrate immune system is characterized by the evolution of acquired immunity in addition to innate immunity. Acquired immunity is mediated by T and B cells, which utilize rearranged receptors. This system is advantageous for detecting pathogens with high specificity, eradicating infection in the late stages and establishing an immunological memory. However, the mammalian innate immune system plays critical roles in the initial defense against invading pathogens and subsequent activation of the acquired immune system. Innate immune cells, such as macrophages and dendritic cells (DCs), sense pathogens through TLRs, phagocytose them and evoke immune responses.

To date, 12 different TLRs have been reported in either humans or mice. The innate immunity system targets a set of molecular structures that are unique to microorganisms and shared by various pathogens, but absent from host cells. By recognizing these “pathogen-specific” patterns, the innate immunity system is able to prevent autoimmune responses. Members of the TLR family of proteins are characterized by extracellular leucine-rich repeat (LRR) motifs responsible for ligand recognition, a transmembrane region and a cytoplasmic tail containing a Toll/IL-1 receptor homology (TIR) domain.

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Type: Chapter
Information: Dendritic Cell Interactions with Bacteria , pp. 27 - 50
DOI: https://doi.org/10.1017/CBO9780511541551.003 [Opens in a new window]
Publisher: Cambridge University Press
Print publication year: 2007

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References

Akira, S. and Takeda, K. (2004). Toll-like receptor signalling. Nat. Rev. Immunol. 4: 499–511CrossRef Google Scholar PubMed

Beutler, B. (2004). Inferences, questions and possibilities in Toll-like receptor signalling. Nature 430: 257–63CrossRef Google Scholar PubMed

Poltorak, A., He, X., Smirnova, I., Liu, M. Y., Huffel, C., Du, X., Birdwell, D., Alejos, E., Silva, M., Galanos, C., Freudenberg, M., Ricciardi-Castagnoli, P., Layton, B., and Beutler, B. (1998). Defective lipopolysaccharide signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 282: 2085–8CrossRef Google Scholar PubMed

Hoshino, K., Takeuchi, O., Kawai, T., Sanjo, H., Ogawa, T., Takeda, Y., Takeda, K., and Akira, S. (1999). Cutting edge: Toll-like receptor 4 (Toll-like receptor4)- deficient mice are hyporesponsive to lipopolysaccharide: evidence for Toll-like receptor4 as the Lps gene product. J. Immunol. 162: 3749–52Google Scholar

Takeuchi, O., Hoshino, K., Kawai, T., Sanjo, H., Takada, H., Ogawa, T., Takeda, K., and Akira, S. (1999). Differential roles of Toll-like receptor2 and Toll-like receptor4 in recognition of Gram-negative and Gram-positive bacterial cell wall components. Immunity 11: 443–51CrossRef Google Scholar

Takeuchi, O., Kawai, T., Muhlradt, P. F., Morr, M., Radolf, J. D., Zychlinsky, A., Takeda, K., and Akira, S. (2001). Discrimination of bacterial lipoproteins by Toll-like receptor 6. Int. Immunol. 13: 933–40CrossRef Google Scholar PubMed

Takeuchi, O., Sato, S., Horiuchi, T., Hoshino, K., Takeda, K., Dong, Z., Modlin, R. L., and Akira, S. (2002). Cutting edge: role of Toll-like receptor 1 in mediating immune response to microbial lipoproteins. J. Immunol. 169: 10–14CrossRef Google Scholar PubMed

Alexopoulou, L., Thomas, V., Schnare, M., Lobet, Y., Anguita, J., Schoen, R. T., Medzhitov, R., Fikrig, E., and Flavell, R. A. (2002). Hyporesponsiveness to vaccination with Borrelia burgdorferi OspA in humans and in Toll-like receptor1- and Toll-like receptor2-deficient mice. Nat. Med. 8: 878–84CrossRef Google Scholar

Hayashi, F., Smith, K. D., Ozinsky, A., Hawn, T. R., Yi, E. C., Goodlett, D. R., Eng, J. K., Akira, S., Underhill, D. M., and Aderem, A. (2001). The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature 410: 1099–103CrossRef Google Scholar PubMed

Zhang, D., Zhang, G., Hayden, M. S., Greenblatt, M. B., Bussey, C., Flavell, R. A., and Ghosh, S. (2004). A toll-like receptor that prevents infection by uropathogenic bacteria. Science 303: 1522–6CrossRef Google Scholar PubMed

Yarovinsky, F., Zhang, D., Andersen, J. F., Bannenberg, G. L., Serhan, C. N., Hayden, M. S., Hieny, S., Sutterwala, F. S., Flavell, R. A., Ghosh, S., and Sher, A. (2005). Toll-like receptor11 Activation of dendritic cells by a protozoan profilin-like protein. Science 308: 1626–9CrossRef Google Scholar PubMed

Alexopoulou, L., Holt, A. C., Medzhitov, R., and Flavell, R. A. (2001). Recognition of double-stranded RNA and activation of nuclear factor-kappaB by Toll-like receptor 3. Nature 413: 732–8CrossRef Google Scholar

Heil, F., Hemmi, H., Hochrein, H., Ampenberger, F., Kirschning, C., Akira, S., Lipford, G., Wagner, H., and Bauer, S. (2004). Species-specific recognition of single-stranded RNA via Toll-like receptor 7 and 8. Science 303: 1526–9CrossRef Google Scholar PubMed

Diebold, S. S., Kaisho, T., Hemmi, H., Akira, S., and Sousa, C. Reis e (2004). Innate antiviral responses by means of Toll-like receptor7-mediated recognition of single-stranded RNA. Science 303: 1529–31CrossRef Google Scholar PubMed

Hemmi, H., Takeuchi, O., Kawai, T., Kaisho, T., Sato, S., Sanjo, H., Matsumoto, M., Hoshino, K., Wagner, H., Takeda, K., and Akira, S. (2000). A Toll-like receptor recognizes bacterial DNA. Nature 408: 740–5CrossRef Google Scholar PubMed

Lund, J., Sato, A., Akira, S., Medzhitov, R., and Iwasaki, A. (2003). Toll-like receptor 9-mediated recognition of Herpes simplex virus-2 by plasmacytoid dendritic cells. J. Exp. Med. 198: 513–20CrossRef Google Scholar PubMed

Krug, A., Luker, G. D., Barchet, W., Leib, D. A., Akira, S., and Colonna, M. (2004). Herpes simplex virus type 1 activates murine natural interferon-producing cells through Toll-like receptor 9. Blood 103: 1433–7CrossRef Google Scholar PubMed

Latz, E., Schoenemeyer, A., Visintin, A., Fitzgerald, K. A., Monks, B. G., Knetter, C. F., Lien, E., Nilsen, N. J., Espevik, T., and Golenbock, D. T. (2004). Toll-like receptor9 signals after translocating from the endoplasmic reticulum to CpG DNA in the lysosome. Nat. Immunol. 5: 190–8CrossRef Google Scholar

Couillault, C., Pujol, N., Reboul, J., Sabatier, L., Guichou, J. F., Kohara, Y., and Ewbank, J. J. (2004). Toll-like receptor-independent control of innate immunity in Caenorhabditis elegans by the Toll/interleukin1 receptor domain adaptor protein Toll/interleukin1 receptor-1, an ortholog of human sterile α and HEAT-Armadillo motif. Nat. Immunol. 5: 488–94CrossRef Google Scholar

Liberati, N. T., Fitzgerald, K. A., Kim, D. H., Feinbaum, R., Golenbock, D. T., and Ausubel, F. M. (2004). Requirement for a conserved Toll/interleukin-1 resistance domain protein in the Caenorhabditis elegans immune response. Proc. Natl Acad. Sci. U S A 101: 6593–8CrossRef Google Scholar PubMed

Muzio, M., Ni, J., Feng, P., and Dixit, V. M. (1997). interleukin-1R-associated kinase (Pelle) family member interleukin-1R-associated kinase-2 and MyD88 as proximal mediators of interleukin-1 signaling. Science 278: 1612–15CrossRef Google Scholar

Wesche, H., Henzel, W. J., Shillinglaw, W., Li, S., and Cao, Z. (1997). MyD88: an adapter that recruits interleukin-1R-associated kinase to the interleukin-1 receptor complex. Immunity 7: 837–47CrossRef Google Scholar

Adachi, O., Kawai, T., Takeda, K., Matsumoto, M., Tsutsui, H., Sakagami, M., Nakanishi, K., and Akira, S. (1998). Targeted disruption of the MyD88 gene results in loss of interleukin-1- and interleukin-18-mediated function. Immunity 9: 143–50CrossRef Google Scholar

Kawai, T., Adachi, O., Ogawa, T., Takeda, K., and Akira, S. (1999). Unresponsiveness of MyD88-deficient mice to endotoxin. Immunity 11: 115–22CrossRef Google Scholar PubMed

Takeuchi, O., Takeda, K., Hoshino, K., Adachi, O., Ogawa, T., and Akira, S. (2000). Cellular responses to bacterial cell wall components are mediated through MyD88-dependent signaling cascades. Int. Immunol. 12: 113–17CrossRef Google Scholar PubMed

Horng, T., Barton, G. M., and Medzhitov, R. (2001). Toll/interleukin1 receptorAP: an adapter molecule in the Toll signaling pathway. Nat. Immunol. 2: 835–41CrossRef Google Scholar

Fitzgerald, K. A., Palsson-McDermott, E. M., Bowie, A. G., Jefferies, C. A., Mansell, A. S., Brady, G., Brint, E., Dunne, A., Gray, P., Harte, M. T., McMurray, D., Smith, D. E., Sims, J. E., Bird, T. A., and O'Neill, L. A. (2001). Mal (MyD88-adapter-like) is required for Toll-like receptor-4 signal transduction. Nature 413: 78–83CrossRef Google Scholar PubMed

Horng, T., Barton, G. M., Flavell, R. A., and Medzhitov, R. (2002). The adaptor molecule Toll/interleukin1 receptorAP provides signalling specificity for Toll-like receptors. Nature 420: 329–33CrossRef Google Scholar

Yamamoto, M., Sato, S., Hemmi, H., Sanjo, H., Uematsu, S., Kaisho, T., Hoshino, K., Takeuchi, O., Kobayashi, M., Fujita, T., Takeda, K., and Akira, S. (2002). Essential role for Toll/interleukin1 receptorAP in activation of the signalling cascade shared by Toll-like receptor2 and Toll-like receptor4. Nature 420: 324–9CrossRef

Li, S., Strelow, A., Fontana, E. J., and Wesche, H. (2002). interleukin-1R-associated kinase-4: a novel member of the interleukin-1R-associated kinase family with the properties of an interleukin-1R-associated kinase-kinase. Proc. Natl Acad. Sci. U S A 99: 5567–72CrossRef Google Scholar

Suzuki, N., Suzuki, S., Duncan, G. S., Millar, D. G., Wada, T., Mirtsos, C., Takada, H., Wakeham, A., Itie, A., Li, S., Penninger, J. M., Wesche, H., Ohashi, P. S., Mak, T. W., and Yeh, W. C. (2002). Severe impairment of interleukin-1 and Toll-like receptor signalling in mice lacking interleukin-1R-associated kinase-4. Nature 416: 750–6CrossRef Google Scholar

Thomas, J. A., Allen, J. L., Tsen, M., Dubnicoff, T., Danao, J., Liao, X. C., Cao, Z., and Wasserman, S. A. (1999). Impaired cytokine signaling in mice lacking the interleukin-1 receptor-associated kinase. J. Immunol. 163: 978–84Google Scholar

Swantek, J. L., Tsen, M. F., Cobb, M. H., and Thomas, J. A. (2000). interleukin-1 receptor-associated kinase modulates host responsiveness to endotoxin. J. Immunol. 164: 4301–6CrossRef Google Scholar PubMed

Jiang, Z., Ninomiya-Tsuji, J., Qian, Y., Matsumoto, K., and Li, X. (2002). Interleukin-1 (interleukin-1) receptor-associated kinase-dependent interleukin-1-induced signaling complexes phosphorylate transforming growth factorβ-activating kinase1 and TAB2 at the plasma membrane and activate transforming growth factorβ-activating kinase1 in the cytosol. Mol. Cell Biol. 22: 7158–67CrossRef Google Scholar

Deng, L., Wang, C., Spencer, E., Yang, L., Braun, A., You, J., Slaughter, C., Pickart, C., and Chen, Z. J. (2000). Activation of the IkappaB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain. Cell 103: 351–61CrossRef Google Scholar

Wang, C., Deng, L., Hong, M., Akkaraju, G. R., Inoue, J., and Chen, Z. J. (2001). transforming growth factorβ-activating kinase1 is a ubiquitin-dependent kinase of MKK and IκB kinase. Nature 412: 346–51CrossRef Google Scholar

Ishitani, T., Takaesu, G., Ninomiya-Tsuji, J., Shibuya, H., Gaynor, R. B., and Matsumoto, K. (2003). Role of the TAB2-related protein TAB3 in interleukin-1 and Tnuclear factor signaling. EMBO J. 22: 6277–88CrossRef Google Scholar

Kanayama, A., Seth, R. B., Sun, L., Ea, C. K., Hong, M., Shaito, A., Chiu, Y. H., Deng, L., and Chen, Z. J. (2004). TAB2 and TAB3 activate the nuclear factor-kappaB pathway through binding to polyubiquitin chains. Mol. Cell 15: 535–48CrossRef Google Scholar

Sanjo, H., Takeda, K., Tsujimura, T., Ninomiya-Tsuji, J., Matsumoto, K., and Akira, S. (2003). TAB2 is essential for prevention of apoptosis in fetal liver but not for interleukin-1 signaling. Mol. Cell Biol. 23: 1231–8CrossRef Google Scholar

Hayden, M. S. and Ghosh, S. (2004). Signaling to nuclear factor-kappaB. Genes Dev. 18: 2195–224CrossRef Google Scholar

McDermott, E. P. and O'Neill, L. A. (2002). Ras participates in the activation of p38 MAPK by interleukin-1 by associating with interleukin-1R-associated kinase, interleukin-1R-associated kinase2, TRAF6, and transforming growth factorβ-activating kinase-1. J. Biol. Chem. 277: 7808–15CrossRef Google Scholar

Matsuzawa, A., Saegusa, K., Noguchi, T., Sadamitsu, C., Nishitoh, H., Nagai, S., Koyasu, S., Matsumoto, K., Takeda, K., and Ichijo, H. (2005). ROS-dependent activation of the TRAF6-ASK1-p38 pathway is selectively required for Toll-like receptor4-mediated innate immunity. Nat. Immunol. 6: 587–92CrossRef Google Scholar PubMed

Takaoka, A., Yanai, H., Kondo, S., Duncan, G., Negishi, H., Mizutani, T., Kano, S., Honda, K., Ohba, Y., Mak, T. W., and Taniguchi, T. (2005). Integral role of interferon regulatory factor-5 in the gene induction programme activated by Toll-like receptors. Nature 434: 243–9CrossRef Google Scholar

Schoenemeyer, A., Barnes, B. J., Mancl, M. E., Latz, E., Goutagny, N., Pitha, P. M., Fitzgerald, K. A., and Golenbock, D. T. (2005). The interferon regulatory factor, interferon regulatory factor5, is a central mediator of toll-like receptor 7 signaling. J. Biol. Chem. 280: 17005–12CrossRef Google Scholar

Brint, E. K., Xu, D., Liu, H., Dunne, A., McKenzie, A. N., O'Neill, L. A., and Liew, F. Y. (2004). ST2 is an inhibitor of interleukin 1 receptor and Toll-like receptor 4 signaling and maintains endotoxin tolerance. Nat. Immunol. 5: 373–9CrossRef Google Scholar PubMed

Divanovic, S., Trompette, A., Atabani, S. F., Madan, R., Golenbock, D. T., Visintin, A., Finberg, R. W., Tarakhovsky, A., Vogel, S. N., Belkaid, Y., Kurt-Jones, E. A., and Karp, C. L. (2005). Negative regulation of Toll-like receptor 4 signaling by the Toll-like receptor homolog RP105. Nat. Immunol. 6: 571–8CrossRef Google Scholar PubMed

Nagai, Y., Kobayashi, T., Motoi, Y., Ishiguro, K., Akashi, S., Saitoh, S., Kusumoto, Y., Kaisho, T., Akira, S., Matsumoto, M., Takatsu, K., and Miyake, K. (2005). The radioprotective 105/MD-1 complex links Toll-like receptor2 and Toll-like receptor4/MD-2 in antibody response to microbial membranes. J. Immunol. 174: 7043–9CrossRef Google Scholar

Chuang, T. H. and Ulevitch, R. J. (2004). Triad3A, an E3 ubiquitin-protein ligase regulating Toll-like receptors. Nat. Immunol. 5: 495–502CrossRef Google Scholar PubMed

Hamerman, J. A., Tchao, N. K., Lowell, C. A., and Lanier, L. L. (2005). Enhanced Toll-like receptor responses in the absence of signaling adaptor DAP12. Nat. Immunol. 6: 579–86CrossRef Google Scholar PubMed

Burns, K., Janssens, S., Brissoni, B., Olivos, N., Beyaert, R., and Tschopp, J. (2003). Inhibition of interleukin 1 receptor/Toll-like receptor signaling through the alternatively spliced, short form of MyD88 is due to its failure to recruit interleukin-1R-associated kinase-4. J. Exp. Med. 197: 263–8CrossRef Google Scholar

Burns, K., Clatworthy, J., Martin, L., Martinon, F., Plumpton, C., Maschera, B., Lewis, A., Ray, K., Tschopp, J., and Volpe, F. (2000). Tollip, a new component of the interleukin-1RI pathway, links interleukin-1R-associated kinase to the interleukin-1 receptor. Nat. Cell Biol. 2: 346–51CrossRef Google Scholar

Zhang, G. and Ghosh, S. (2002). Negative regulation of Toll-like receptor-mediated signaling by Tollip. J. Biol. Chem. 277: 7059–65CrossRef Google Scholar PubMed

Boone, D. L., Turer, E. E., Lee, E. G., Ahmad, R. C., Wheeler, M. T., Tsui, C., Hurley, P., Chien, M., Chai, S., Hitotsumatsu, O., McNally, E., Pickart, C., and Ma, A. (2004). The ubiquitin-modifying enzyme A20 is required for termination of Toll-like receptor responses. Nat. Immunol. 5: 1052–60CrossRef Google Scholar PubMed

Yamamoto, M., Sato, S., Mori, K., Hoshino, K., Takeuchi, O., Takeda, K., and Akira, S. (2002). Cutting edge: a novel Toll/interleukin-1 receptor domain-containing adapter that preferentially activates the interferon-beta promoter in the Toll-like receptor signaling. J. Immunol. 169: 6668–72CrossRef Google Scholar

Oshiumi, H., Matsumoto, M., Funami, K., Akazawa, T., and Seya, T. (2003). TICAM-1, an adaptor molecule that participates in Toll-like receptor 3-mediated interferon-beta induction. Nat. Immunol. 4: 161–7CrossRef Google Scholar PubMed

Sharma, S., tenOever, B. R., Grandvaux, N., Zhou, G. P., Lin, R., and Hiscott, J. (2003). Triggering the interferon antiviral response through an IκB kinase-related pathway. Science 300: 1148–51CrossRef Google Scholar

Fitzgerald, K. A., McWhirter, S. M., Faia, K. L., Rowe, D. C., Latz, E., Golenbock, D. T., Coyle, A. J., Liao, S. M., and Maniatis, T. (2003). IκB kinaseepsilon and TBK1 are essential components of the interferon regulatory factor3 signaling pathway. Nat. Immunol. 4: 491–6CrossRef Google Scholar

Hemmi, H., Takeuchi, O., Sato, S., Yamamoto, M., Kaisho, T., Sanjo, H., Kawai, T., Hoshino, K., Takeda, K., and Akira, S. (2004). The roles of two IkappaB kinase-related kinases in lipopolysaccharide and double stranded RNA signaling and viral infection. J. Exp. Med. 199: 1641–50CrossRef Google Scholar PubMed

McWhirter, S. M., Fitzgerald, K. A., Rosains, J., Rowe, D. C., Golenbock, D. T., and Maniatis, T. (2004). interferon-regulatory factor 3-dependent gene expression is defective in Tbk1-deficient mouse embryonic fibroblasts. Proc. Natl Acad. Sci. U S A 101: 233–8CrossRef Google Scholar PubMed

Perry, A. K., Chow, E. K., Goodnough, J. B., Yeh, W. C., and Cheng, G. (2004). Differential requirement for TAnatural killer-binding kinase-1 in type I interferon responses to Toll-like receptor activation and viral infection. J. Exp. Med. 199: 1651–8CrossRef Google Scholar

Yoneyama, M., Suhara, W., Fukuhara, Y., Fukuda, M., Nishida, E., and Fujita, T. (1998). Direct triggering of the type I interferon system by virus infection: activation of a transcription factor complex containing interferon regulatory factor-3 and CBP/p300. EMBO J. 17: 1087–95CrossRef Google Scholar PubMed

Sakaguchi, S., Negishi, H., Asagiri, M., Nakajima, C., Mizutani, T., Takaoka, A., Honda, K., and Taniguchi, T. (2003). Essential role of interferon regulatory factor-3 in lipopolysaccharide-induced interferon-beta gene expression and endotoxin shock. Biochem. Biophys. Res. Commun. 306: 860–6CrossRef Google Scholar PubMed

Honda, K., Yanai, H., Negishi, H., Asagiri, M., Sato, M., Mizutani, T., Shimada, N., Ohba, Y., Takaoka, A., Yoshida, N., and Taniguchi, T. (2005). interferon regulatory factor-7 is the master regulator of type-I interferon-dependent immune responses. Nature 434: 772–7CrossRef Google Scholar PubMed

Sato, S., Sugiyama, M., Yamamoto, M., Watanabe, Y., Kawai, T., Takeda, K., and Akira, S. (2003). Toll/interleukin-1 receptor domain-containing adaptor inducing interferon-beta (Toll/IL1 receptor domain-containing adaptor inducing interferonβ) associates with Tnuclear factor receptor-associated factor 6 and TAnatural killer-binding kinase 1, and activates two distinct transcription factors, nuclear factor-kappa B and interferon-regulatory factor-3, in the Toll-like receptor signaling. J. Immunol. 171: 4304–10CrossRef Google Scholar

Meylan, E., Burns, K., Hofmann, K., Blancheteau, V., Martinon, F., Kelliher, M., and Tschopp, J. (2004). RIP1 is an essential mediator of Toll-like receptor 3-induced nuclear factor-kappaB activation. Nat. Immunol. 5: 503–7CrossRef Google Scholar

Han, K. J., Su, X., Xu, L. G., Bin, L. H., Zhang, J., and Shu, H. B. (2004). Mechanisms of the Toll/IL1 receptor domain-containing adaptor inducing interferonβ-induced interferon-stimulated response element and nuclear factor-kappaB activation and apoptosis pathways. J. Biol. Chem. 279: 15652–61CrossRef Google Scholar

Kaiser, W. J. and Offermann, M. K. (2005). Apoptosis induced by the toll-like receptor adaptor Toll/IL1 receptor domain-containing adaptor inducing interferonβ is dependent on its receptor interacting protein homotypic interaction motif. J. Immunol. 174: 4942–52CrossRef Google Scholar

Yamamoto, M., Sato, S., Hemmi, H., Hoshino, K., Kaisho, T., Sanjo, H., Takeuchi, O., Sugiyama, M., Okabe, M., Takeda, K., and Akira, S. (2003). Role of adaptor Toll/IL1 receptor domain-containing adaptor inducing interferonβ in the MyD88-independent toll-like receptor signaling pathway. Science 301: 640–3CrossRef Google Scholar

Hirotani, T., Yamamoto, M., Kumagai, Y., Uematsu, S., Kawase, I., Takeuchi, O., and Akira, S. (2005). Regulation of lipopolysaccharide-inducible genes by MyD88 and Toll/interleukin-1 domain containing adaptor inducing interferon-beta. Biochem. Biophys. Res. Commun. 328: 383–92CrossRef Google Scholar

Fitzgerald, K. A., Rowe, D. C., Barnes, B. J., Caffrey, D. R., Visintin, A., Latz, E., Monks, B., Pitha, P. M., and Golenbock, D. T. (2003). lipopolysaccharide-Toll-like receptor4 signaling to interferon regulatory factor-3/7 and nuclear factor-kappaB involves the toll adapters Toll/IL1 receptor domain-containing adaptor inducing interferonβ-related adaptor molecule and Toll/IL1 receptor domain-containing adaptor inducing interferonβ. J. Exp. Med. 198: 1043–55CrossRef Google Scholar

Yamamoto, M., Sato, S., Hemmi, H., Uematsu, S., Hoshino, K., Kaisho, T., Takeuchi, O., Takeda, K., and Akira, S. (2003). Toll/IL1 receptor domain-containing adaptor inducing interferonβ-related adaptor molecule is specifically involved in the Toll-like receptor 4-mediated MyD88-independent signaling pathway. Nat. Immunol. 4: 1144–50CrossRef Google Scholar

Liu, Y. J. (2005). IPC: Professional type 1 interferon-producing cells and plasmacytoid dendritic cell precursors. Annu. Rev. Immunol. 23: 275–306CrossRef Google Scholar PubMed

Hemmi, H., Kaisho, T., Takeda, K., and Akira, S. (2003). The roles of Toll-like receptor 9, MyD88, and DNA-dependent protein kinase catalytic subunit in the effects of two distinct CpG DNAs on dendritic cell subsets. J. Immunol. 170: 3059–64CrossRef Google Scholar PubMed

Hochrein, H., Schlatter, B., O'Keeffe, M., Wagner, C., Schmitz, F., Schiemann, M., Bauer, S., Suter, M., and Wagner, H. (2004). Herpes simplex virus type-1 induces interferon-alpha production via Toll-like receptor 9-dependent and -independent pathways. Proc. Natl Acad. Sci. U S A 101: 11416–21CrossRef Google Scholar PubMed

Kawai, T., Sato, S., Ishii, K. J., Coban, C., Hemmi, H., Yamamoto, M., Terai, K., Matsuda, M., Inoue, J., Uematsu, S., Takeuchi, O., and Akira, S. (2004). Interferon-alpha induction through Toll-like receptors involves a direct interaction of interferon regulatory factor7 with MyD88 and TRAF6. Nat. Immunol. 5: 1061–8CrossRef Google Scholar

Honda, K., Yanai, H., Mizutani, T., Negishi, H., Shimada, N., Suzuki, N., Ohba, Y., Takaoka, A., Yeh, W. C., and Taniguchi, T. (2004). Role of a transductional-transcriptional processor complex involving MyD88 and interferon regulatory factor-7 in Toll-like receptor signaling. Proc. Natl Acad. Sci. U S A 101: 15416–21CrossRef Google Scholar PubMed

Uematsu, S., Sato, S., Yamamoto, M., Hirotani, T., Kato, H., Takeshita, F., Matsuda, M., Coban, C., Ishii, K. J., Kawai, T., Takeuchi, O., and Akira, S. (2005). Interleukin-1 receptor-associated kinase-1 plays an essential role for Toll-like receptor (Toll-like receptor)7- and Toll-like receptor9-mediated interferon-{alpha} induction. J. Exp. Med. 201: 915–23CrossRef Google Scholar PubMed

Kerkmann, M., Rothenfusser, S., Hornung, V., Towarowski, A., Wagner, M., Sarris, A., Giese, T., Endres, S., and Hartmann, G. (2003). Activation with CpG-A and CpG-B oligonucleotides reveals two distinct regulatory pathways of type I interferon synthesis in human plasmacytoid dendritic cells. J. Immunol. 170: 4465–74CrossRef Google Scholar PubMed

Honda, K., Ohba, Y., Yanai, H., Negishi, H., Mizutani, T., Takaoka, A., Taya, C., and Taniguchi, T. (2005). Spatiotemporal regulation of MyD88-interferon regulatory factor-7 signalling for robust type-I interferon induction. Nature 434: 1035–40CrossRef Google Scholar PubMed

Diebold, S. S., Montoya, M., Unger, H., Alexopoulou, L., Roy, P., Haswell, L. E., Al-Shamkhani, A., Flavell, R., Borrow, P., and Sousa, C. Reis e (2003). Viral infection switches non-plasmacytoid dendritic cells into high interferon producers. Nature 424: 324–8CrossRef Google Scholar PubMed

Smith, E. J., Marie, I., Prakash, A., Garcia-Sastre, A., and Levy, D. E. (2001). interferon regulatory factor3 and interferon regulatory factor7 phosphorylation in virus-infected cells does not require double-stranded RNA-dependent protein kinase R or Ikappa B kinase but is blocked by Vaccinia virus E3L protein. J. Biol. Chem. 276: 8951–7CrossRef Google Scholar PubMed

Yoneyama, M., Kikuchi, M., Natsukawa, T., Shinobu, N., Imaizumi, T., Miyagishi, M., Taira, K., Akira, S., and Fujita, T. (2004). The RNA helicase retinoic acid-inducible protein-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nat. Immunol. 5: 730–7CrossRef Google Scholar

Andrejeva, J., Childs, K. S., Young, D. F., Carlos, T. S., Stock, N., Goodbourn, S., and Randall, R. E. (2004). The V proteins of paramyxoviruses bind the interferon-inducible RNA helicase, mda-5, and inhibit its activation of the interferon-beta promoter. Proc. Natl Acad. Sci. U S A 101: 17264–9CrossRef Google Scholar

Kato, H., Sato, S., Yoneyama, M., Yamamoto, M., Uematsu, S., Matsui, K., Tsujimura, T., Takada, K., Fujita, T., Takeuchi, O., and Akira, S. (2005). Cell type-specific involvement of retinoic acid-inducible protein-I in antiviral response. Immunity 23: 19–28.CrossRef

Balachandran, S., Thomas, E., and Barber, G. N. (2004). A Fas (Tnuclear factorRSF6)-associated via death domain-dependent innate immune mechanism in mammalian cells. Nature 432: 401–5CrossRef Google Scholar

Girardin, S. E., Boneca, I. G., Carneiro, L. A., Antignac, A., Jehanno, M., Viala, J., Tedin, K., Taha, M. K., Labigne, A., Zahringer, U., Coyle, A. J., DiStefano, P. S., Bertin, J., Sansonetti, P. J., and Philpott, D. J. (2003). Nod1 detects a unique muropeptide from Gram-negative bacterial peptidoglycan. Science 300: 1584–7CrossRef Google Scholar PubMed

Chamaillard, M., Hashimoto, M., Horie, Y., Masumoto, J., Qiu, S., Saab, L., Ogura, Y., Kawasaki, A., Fukase, K., Kusumoto, S., Valvano, M. A., Foster, S. J., Mak, T. W., Nunez, G., and Inohara, N. (2003). An essential role for nucleotide-binding oligomerization domain1 in host recognition of bacterial peptidoglycan containing diaminopimelic acid. Nat. Immunol. 4: 702–7CrossRef Google Scholar

Girardin, S. E., Boneca, I. G., Viala, J., Chamaillard, M., Labigne, A., Thomas, G., Philpott, D. J., and Sansonetti, P. J. (2003). Nod2 is a general sensor of peptidoglycan through muramyl dipeptide (muramyl dipeptide) detection. J. Biol. Chem. 278: 8869–72CrossRef Google Scholar PubMed

Ogura, Y., Bonen, D. K., Inohara, N., Nicolae, D. L., Chen, F. F., Ramos, R., Britton, H., Moran, T., Karaliuskas, R., Duerr, R. H., Achkar, J. P., Brant, S. R., Bayless, T. M., Kirschner, B. S., Hanauer, S. B., Nunez, G., and Cho, J. H. (2001). A frameshift mutation in nucleotide-binding oligomerization domain2 associated with susceptibility to Crohn's disease. Nature 411: 603–6CrossRef Google Scholar

Kobayashi, K. S., Chamaillard, M., Ogura, Y., Henegariu, O., Inohara, N., Nunez, G., and Flavell, R. A. (2005). Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract. Science 307: 731–4CrossRef Google Scholar PubMed

Watanabe, T., Kitani, A., Murray, P. J., and Strober, W. (2004). nucleotide-binding oligomerization domain2 is a negative regulator of Toll-like receptor 2-mediated T helper type 1 responses. Nat. Immunol. 5: 800–8CrossRef Google Scholar

Maeda, S., Hsu, L. C., Liu, H., Bankston, L. A., Iimura, M., Kagnoff, M. F., Eckmann, L., and Karin, M. (2005). Nod2 mutation in Crohn's disease potentiates nuclear factor-kappaB activity and interleukin-1beta processing. Science 307: 734–8CrossRef Google Scholar

Kobayashi, K., Inohara, N., Hernandez, L. D., Galan, J. E., Nunez, G., Janeway, C. A., Medzhitov, R., and Flavell, R. A. (2002). Rip-like interacting caspase-like apoptosis-regulatory protein kinase/Rip2/CARDIAK mediates signalling for receptors of the innate and adaptive immune systems. Nature 416: 194–9CrossRef Google Scholar

Inohara, N., Chamaillard, M., McDonald, C., and Nunez, G. (2005). nucleotide-binding oligomerization domain-leucine-rich repeat proteins: role in host-microbial interactions and inflammatory disease. Annu. Rev. Biochem. 74: 355–83CrossRef Google Scholar

Bowie, A., Kiss-Toth, E., Symons, J. A., Smith, G. L., Dower, S. K., and O'Neill, L. A. (2000). A46R and A52R from vaccinia virus are antagonists of host interleukin-1 and toll-like receptor signaling. Proc. Natl Acad. Sci. U S A 97: 10162–7CrossRef Google Scholar PubMed

Stack, J., Haga, I. R., Schroder, M., Bartlett, N. W., Maloney, G., Reading, P. C., Fitzgerald, K. A., Smith, G. L., and Bowie, A. G. (2005). Vaccinia virus protein A46R targets multiple Toll-like-interleukin-1 receptor adaptors and contributes to virulence. J. Exp. Med. 201: 1007–18CrossRef Google Scholar PubMed

DiPerna, G., Stack, J., Bowie, A. G., Boyd, A., Kotwal, G., Zhang, Z., Arvikar, S., Latz, E., Fitzgerald, K. A., and Marshall, W. L. (2004). Poxvirus protein N1L targets the I-kappaB kinase complex, inhibits signaling to nuclear factor-kappaB by the tumor necrosis factor superfamily of receptors, and inhibits nuclear factor-kappaB and interferon regulatory factor3 signaling by toll-like receptors. J. Biol. Chem. 279: 36570–8CrossRef Google Scholar

Li, K., Foy, E., Ferreon, J. C., Nakamura, M., Ferreon, A. C., Ikeda, M., Ray, S. C., Gale, M. Jr., and Lemon, S. M. (2005). Immune evasion by hepatitis C virus NS3/4A protease-mediated cleavage of the Toll-like receptor 3 adaptor protein Toll/IL1 receptor domain-containing adaptor inducing interferonβ. Proc. Natl Acad. Sci. U S A 102: 2992–7CrossRef Google Scholar

Breiman, A., Grandvaux, N., Lin, R., Ottone, C., Akira, S., Yoneyama, M., Fujita, T., Hiscott, J., and Meurs, E. F. (2005). Inhibition of retinoic acid-inducible protein-I-dependent signaling to the interferon pathway during hepatitis C virus expression and restoration of signaling by IκB kinaseepsilon. J. Virol. 79: 3969–78CrossRef Google Scholar

Fortune, S. M., Solache, A., Jaeger, A., Hill, P. J., Belisle, J. T., Bloom, B. R., Rubin, E. J., and Ernst, J. D. (2004). Mycobacterium tuberculosis inhibits macrophage responses to interferon-gamma through myeloid differentiation factor 88-dependent and -independent mechanisms. J. Immunol. 172: 6272–80CrossRef Google Scholar PubMed

Netea, M. G., Sutmuller, R., Hermann, C., Graaf, C. A., Meer, J. W., Krieken, J. H., Hartung, T., Adema, G., and Kullberg, B. J. (2004). Toll-like receptor 2 suppresses immunity against Candida albicans through induction of interleukin-10 and regulatory T cells. J. Immunol. 172: 3712–18CrossRef Google Scholar PubMed

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