Fearon, D.T. Seeking wisdom in innate immunity. Nature 388, 323–324 (1997).
Medzhitov, R., Preston-Hurburt, P. & Janeway, C.A., Jr. A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 388, 394–397 (1997).
Imler, J.L. & Hoffmann, J.A. Toll receptors in innate immunity. Trends Cell Biol. 11, 304–311 (2001).
Aderem, A. & Ulevitch, R.J. Toll-like receptors in the induction of the innate immune response. Nature 406, 782–787 (2000).
Rock, F.L., Hardiman, G., Timans, J.C., Kastelein, R.A. & Bazan, J.F.A. A family of human receptors structurally related to Drosophila Toll. Proc. Natl. Acad. Sci. USA 95, 588–593 (1998).
Akira, S., Takeda, K. & Kaisho, T. Toll-like receptors: critical proteins linking innate and acquired immunity. Nat. Immunol. 2, 675–680 (2001).
O'Neill, L.A. & Dinarello, C.A. The IL-1 receptor-Toll-like receptor superfamily: crucial receptors for inflammation and host defense. Immunol. Today 21, 206–209 (2000).
Matsumoto, M., Kikkawa, S., Kohase, M., Miyake, K. & Seya, T. Establishment of a monoclonal antibody against human Toll-like receptor 3 that blocks double-stranded RNA-mediated signaling. Biochem. Biophys. Res. Commun. 293, 1364–1369 (2002).
Hemmi, H. et al. A Toll-like receptor recognizes bacterial DNA. Nature 408, 740–745 (2000).
Hayashi, F. et al. The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature 410, 1099–1103 (2001).
Hemmi, H. et al. Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway. Nat. Immunol. 3, 196–200 (2002).
Kawai, T. et al. Lipopolysaccharide stimulates the MyD88-independent pathway and results in activation of IFN-regulatory factor 3 and the expression of a subset of lipopolysaccharide-inducible genes. J. Immunol. 167, 5887–5894 (2001).
Horng, T., Barton, G.M. & Medzhitov, R. TIRAP: an adaptor molecule in the Toll signaling pathway. Nat. Immunol. 2, 835–841 (2001).
Fitzgerald, K.A. et al. Mal (MyD88-adaptor-like) is required for Toll-like receptor-4 signal transduction. Nature 413, 78–83 (2001).
Yamamoto, M. et al. Essential role for TIRAP in activation of the signalling cascade shared by TLR2 and TLR4. Nature 420, 324–329 (2002).
Horng, T., Barton, G.M., Flavell, R.A. & Medzhitov, R. The adaptor molecule TIRAP provides signalling specificity for Toll-like receptors. Nature 420, 329–333 (2002).
Toshchakov, V. et al. TLR4, but not TLR2, mediates IFN-β-induced STAT1 α/β-dependent gene expression in macrophages. Nat. Immunol. 3, 392–398 (2002).
Alexopoulou, L., Holt, A.C., Medzhitov, R. & Flavell, R.A. Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3. Nature 413, 732–738 (2001).
Muzio, M., Ni, J., Feng, P. & Dixit, V.M. IRAK (Pelle) family member IRAK-2 and MyD88 as proximal mediators of IL-1 signaling. Science 278, 1612–1615 (1997).
Kaisho, T., Takeuchi, O., Kawai, T., Hoshino, K. & Akira, S. Endotoxin-induced maturation of MyD88-deficient dendritic cells. J. Immunol. 166, 5688–5694 (2001).
Xu, Y. et al. Structural basis for signal transduction by the Toll/interleukin-1 receptor domains. Nature 408, 111–115 (2000).
Uehori, J. et al. Simultaneous blocking of human Toll-like receptor 2 and 4 suppresses myeloid dendritic cell maturation induced by Mycobacterium bovis BCG-peptidoglycan. Infect. Immun. (in the press).
Peters, K.L., Smith, H.L., Stark, G.R. & Sen, G.C. IRF-3-dependent, NF-κB- and JNK-independent activation of the 561 and IFN-β genes in response to double-stranded RNA. Proc. Natl. Acad. Sci. USA 99, 6322–6327 (2002).
Yang, Y.-L. et al. Deficient signaling in mice devoid of double-stranded RNA-dependent protein kinase. EMBO J. 14, 6095–6106 (1995).
Taniguchi, T., Ogasawara, K., Takaoka, A. & Tanaka, N. IRF family of transcription factors as regulators of host defense. Annu. Rev. Immunol. 19, 623–655 (2001).
Iwamura, T. et al. Induction of IRF-3/-7 kinase and NF-κB in response to double-stranded RNA and virus infection: common and unique pathways. Genes Cells 6, 375–388 (2001).
Patel, R.C. & Sen, G.C. PACT, a protein activator of the interferon-induced protein kinase, PKR. EMBO J. 17, 4379–4390 (1998).
Chu, W.M. et al. JNK2 and IKKβ are required for activating the innate response to viral infection. Immunity 11, 721–731 (1999).
Maggi, L.B., Jr. et al. Potential role of PKR in double-stranded RNA-induced macrophage activation. EMBO J. 19, 3630–3638 (2000).
Doyle, S. et al. IRF3 mediates a TLR3/TLR4-specific antiviral gene program. Immunity 17, 251–263 (2002).
Muzio, M. et al. Differential expression and regulation of Toll-like receptors (TLR) in human leukocytes: selective expression of TLR3 in dendritic cells. J. Immunol. 164, 5998–6004 (2000).
Cario, E. & Podolsky, D.K. Differential alteration in intestinal epithelial cell expression of Toll-like receptor 3 (TLR3) and TLR4 in inflammatory bowel disease. Infect. Immun. 68, 7010–7017 (2000).
Medzhitov, R. Toll-like receptors and innate immunity. Nat. Rev. Immunol. 1, 135–145 (2001).
Arbibe, L. et al. Toll-like receptor 2-mediated NF-κB activation requires a Rac1-dependent pathway. Nat. Immunol. 1, 533–540 (2000).
Hazeki, K. et al. TLR-mediated tyrosine phosphorylation of paxillin via MyD88-dependent and -independent pathways. Eur. J. Immunol. (in the press).
Cella, M. et al. Maturation, activation, and protection of dendritic cells induced by double-stranded RNA. J. Exp. Med. 189, 821–829 (1999).
Kadowaki, M. et al. Subsets of human dendritic cell precursors express different toll-like receptors and respond to different microbial antigens. J. Exp. Med. 194, 863–870 (2001).
Nishiguchi, M. et al. Mycoplasma fermentans lipoprotein M161Ag-induced cell activation is mediated by Toll-like receptor 2: role of N-terminal hydrophobic portion in its multiple functions. J. Immunol. 166, 2610–2616 (2001).
Shimazu, R. et al. MD-2, a molecule that confers lipopolysaccharide responsiveness on Toll-like receptor 4. J. Exp. Med. 189, 1777–1782 (1999).
Sherman, F., Fink, G.R. & Hicks, J.B. Methods in Yeast Genetics (Cold Spring Harbor Press, Cold Spring Harbor, NY, 1986).
James, P., Halladay, J. & Craig, E.A. Genomic libraries and a host strain designed for highly efficient two-hybrid selection in yeast. Genetics 144, 1425–1436 (1996).
Means, T.K. et al. Human toll-like receptors mediate cellular activation by Mycobacterium tuberculosis. J. Immunol. 163, 3920–3927 (1999).
Elbashir, S.M. et al. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411, 494–498 (2001).
Oshiumi, H., Begum, N.A., Matsumoto, M. & Seya, T. RNA interference for mammalian cells. Nippon Yakurigaku Zasshi 120, 91–95 (2002).