Toll receptors and pathogen resistance

Cellular Microbiology

Volumn 5, Issue 3, 2003, Pages 143-153

  Takeda, Kiyoshi ^a   Akira, Shizuo ^a  

^a OSAKA UNIVERSITY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

ADAPTOR PROTEIN; CYTOKINE; INTERFERON; INTERLEUKIN 1 RECEPTOR; MYELOID DIFFERENTIATION FACTOR 88; TOLL LIKE RECEPTOR; TOLL LIKE RECEPTOR 4; TOLL LIKE RECEPTOR 9; UNCLASSIFIED DRUG;

HOST RESISTANCE; IMMUNE RESPONSE; INSECT; MAMMAL; MICROORGANISM DETECTION; NONHUMAN; PATHOGENICITY; PLANT; PRIORITY JOURNAL; PROTEIN DOMAIN; SHORT SURVEY; SIGNAL TRANSDUCTION; VIRUS DETECTION;

ANIMALS; ANTIGENS, VIRAL; BACTERIAL INFECTIONS; DROSOPHILA; DROSOPHILA PROTEINS; INFECTION; MEMBRANE GLYCOPROTEINS; MICE; MODELS, IMMUNOLOGICAL; PLANTS; RECEPTORS, CELL SURFACE; SIGNAL TRANSDUCTION; TOLL-LIKE RECEPTOR 2; TOLL-LIKE RECEPTOR 3; TOLL-LIKE RECEPTOR 4; TOLL-LIKE RECEPTOR 5; TOLL-LIKE RECEPTORS;

BACTERIA (MICROORGANISMS); HEXAPODA; INSECTA; MAMMALIA;

EID: 0037347050     PISSN: 14625814     EISSN: None     Source Type: Journal    
DOI: 10.1046/j.1462-5822.2003.00264.x     Document Type: Short Survey

References (97)

1. Abel, B., Thieblemont, N., Quesniaux, V.J.F., Brown, N., Mpagi, J., Miyake, K., et al. (2002) Toll-like receptor 4 expression is required to control chronic Mycobacterium tuberculosis infection in mice. J Immunol 169: 3155-3162.
2. Aderem, A., and Underhill, D.M. (1999) Mechanisms of phagocytosis in macrophages. Annu Rev Immunol 17: 593-623.
3. Ahmad-Nejad, P., Hacker, H., Rutz, M., Bauer, S., Vabulas, R.M., and Wagner, H. (2002) Bacterial CpG-DNA and lipopolysaccharides activate Toll-like receptors at distinct cellular compartments. Eur J Immunol 32: 1958-1968.
4. Akira, S., Takeda, K., and Kaisho, T. (2001) Toll-like receptors: critical proteins linking innate and acquired immunity. Nat Immunol 2: 675-680.
5. Alexopoulou, L., Holt, A.C., Medzhitov, R., and Flavell, R.A. (2001) Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3. Nature 413: 732-738.
6. Alexopoulou, L., Thomas, V., Schnare, M., Lobet, Y., Anguita, J., Schoen, R.T., (2002) Hyporesponsiveness to vaccination with Borrelia burgdorferi OspA in humans and in TLR1- and TLR2-deficient mice. Nat Med 8: 878-884.
7. Asea, A., Rehli, M., Kabingu, E., Boch, J.A., Bare, O., Auron, P.E., et al. (2002) Novel signal transduction pathway utilized by extracellular HSP70: role of TLR2 and TLR4. J Biol Chem 277: 15028-15034.
8. Baker, B., Zambryski, P., Staskawicz, B., and Dinesh-Kumar, S.P. (1997) Signaling in plant-microbe interactions. Science 276: 726-733.
9. Bowie, A., Kiss-Toth, E., Symons, J.A., Smith, G.L., Dower, S.K., and O'Neill. L.A.J. (2000) A46R and A52R from vaccinia virus are antagonist of host IL-1 and toll-like receptor signaling. Proc Natl Acad Sci USA 97: 10162-10167.
10. Byrd-Leifer, C.A., Block, E.F., Takeda, K., Akira, S., and Ding, A. (2001) The role of MyD88 and TLR4 in the LPS-mimetic activity of Taxol. Eur J Immunol 31: 2448-2457.
11. Chin, A.I., Dempsey, P.W., Bruhn, K., Miller, J.F., Xu, Y., and Cheng, G. (2002) Involvement of receptor-interacting protein 2 in innate and adaptive immune responses. Nature 416: 190-194.
12. Choe, K.M., Werner, T., Stoven, S., Hultmark, D., and Anderson, K.V. (2002) Requirement of a peptidoglycan recognition protein (PGRP) in Relish activation and antibacterial immune resonses in Drosophila. Science 296: 359-362.
13. Doyle, S.E., Vaidya, S.A., O'Connell, R., Dadgostar, H., Dempsey, P.W., Wu, T.-T., et al. (2002) IRF3 mediates a TLR3/TLR4-specific antiviral gene program. Immunity 17: 251-263.
14. Dybdahl, B., Wahba, A., Lien, E., Flo, T.H., Waage, A., Qureshi, N., et al. (2002) Inflammatory response after open heart surgery: release of heat-shock protein 70 and signaling through toll-like receptor-4. Circulation 105: 685-690.
15. Echchannaoui, H., Frei, K., Schnell, C., Leib, S.L., Zimmerli, W., and Landmann, R. (2002) Toll-like receptor 2-deficient mice are highly susceptible to Streptococcus pneumoniae meningitis because of reduced bacterial clearing and enhanced inflammation. J Infect Dis 186: 798-806.
16. Fearon, D., T., and Locksley, R.M. (1996) The instructive role of innate immunity in the acquired immune responses. Science 272: 50-54.
17. Fitzgerald, K.A., Palsson-McDermott, E.M., Bowie, A.G., Jefferies, C., Mansell, A.S., Brady, G., et al. (2001) Mal (MyD88-adaptor-like) is required for Toll-like receptor-4 signal transduction. Nature 413: 78-83.
18. Gallucci, S., and Matzinger, P. (2001) Danger signals: SOS to the immune system. Curr Opin Immunol 13: 114-119.
19. Georgel, P., Naitza, S., Kappler, C., Ferrandon, D., Zachary, D., Swimmer, C., at al. (2001) Drosophila Immune Deficiency (IMD) is a death domain protein that activates anti-bacterial defence and can promote apoptosis. Dev Cell 1: 503-514.
20. Gewirtz, A.T., Navas, T.A., Lyons, S., Godowski, P.J., and Madara, J.L. (2001) Cutting edge: bacterial flagellin activates basolaterally expressed TLR5 to induce epithelial proinflammatory gene expression. J Immunol 167: 1882-1885.
21. Gomez-Gomez, L., and Boller, T. (2000) FLS2: an LRR receptor-like kinase involved in the perception of the bacterial elicitor flagellin in Arabidopsis. Mol Cell 5: 1003-1011.
22. Gottar, M., Gobert, V., Michel, T., Belvin, M., Duyk, G., Hoffmann, J.A., et al. (2002) The Drosophila immune response against Gram-negative bacteria is mediated by a peptidoglycan recognition protein. Nature 416: 640-644.
23. Hayashi, F., Smith, K.D., Ozinsky, A., Hawn, T.R., Yi, E.C., Goodlett, D.R., et al. (2001) The innate immune response to bacterial flagellin is mediated by Toll-like receptor-5. Nature 410: 1099-1103.
24. Haynes, L.M., Moore, D.D., Kurt-Jones, E.A., Finberg, R.W., Anderson, L.J., and Tripp, R.A. (2001) Involvement of Toll-like receptor 4 in innate immunity to respiratory syncytial virus. J Virol 75: 10730-10737.
25. Haziot, A., Ferrero, E., Kontgen, F., Hijiya, N., Yamamoto, S., Silver, J., et al. (1996) Resistance to endotoxin shock and reduced dissemination of gram negative bacteria in CD14-deficient mice. Immunity 4: 407-414.
26. Hemmi, H., Takeuchi, O., Kawai, T., Kaisho, T., Sato, S., Sanjo, H., et al. (2000) A Toll-like receptor recognizes bacterial DNA. Nature 408: 740-745.
27. Hemmi, H., Kaisho, T., Takeuchi, O., Sato, S., Sanjo, S., Hoshino, K., et al. (2002) Small antiviral compounds activate immune cells via TLR7 MyD88-dependent signalling pathway. Nat Immunol 3: 196-200.
28. Hirschfeld, M., Weis, J.J., Toshchakov, V., Salkowski, C.A., Cody, M.J., Ward, D.C., et al. (2001) Signaling by toll-like receptor 2 and 4 agonists results in differential gene expression in murine macrophages. Infect Immun 69: 1477-1482.
29. Hoffmann, J.A., and Reichhart, J.M. (2002) Drosophila innate immunity: an evolutionary perspective. Nat Immunol 3: 121-126.
30. Hoffmann, J.A., Kafatos, F.C., Janeway, C.A., Jr, and Ezekowiz, R.A.B. (1999) Phylogenetic perspectives in innate immunity. Science 284: 1313-1318.
31. Horng, T., Barton, G.M., and Medzhitov, R. (2001) TIRAP: an adapter molecule in the Toll signaling pathway. Nat Immunol 2: 835-841.
32. Horng, T., Barton, G.M., Flavell, R.A., and Medzhitov, R. (2002) The adaptor molecule TIRAP provides signaling specificity for Toll-like receptors. Nature 420: 329-333.
33. Hoshino, K., Takeuchi, O., Kawai, T., Sanjo, H., Ogawa, T., Takeda, Y., et al. (1999) Cutting Edge: Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the Lps hene product. J Immunol 162: 3749-3752.
34. Hoshino, K., Kaisho, T., Iwabe, T., Takeuchi, O., and Akira, S. (2002) Differential involvement of IFN-β in Toll-like receptor-stimulated dendritic cell activation. Int Immunol 14: 1225-1231.
35. Hu, S., and Yang, X. (2000) dFADD, a novel death domain-containing adapter protein for the Drosophila caspase DREDD. J Biol Chem 275: 30761-30764.
36. Ito, T., Amakawa, R., Kaisho, T., Hemmi, H., Tajima, K., Uehira, K., et al. (2002) Interferon-α and interleukin-12 are induced differentially by Toll-like receptor 7 ligands in human blood dendritic cell subsets. J Exp Med 195: 1507-1512.
37. Jack, R.S., Fan, X., Bernheiden, M., Rune, G., Ehlers, M., Weber, A., et al. (1997) Lipopolysaccharide-binding protein is required to combat a murine gram-negative bacterial infection. Nature 389: 742-745.
38. Jebanathirajah, J., Peri, S., and Pandey, A. (2002) Toll and interleukin-1 receptor (TIR) domain-containing proteins in plants: a genomic perspective. Trends Plant Sci 7: 388-391.
39. Johnson, G.B., Brunn, G.J., Kodaira, Y., and Platt, J.L. (2002) Receptor-mediated monitoring of tissue well-being via detection of soluble heparan sulfate by Toll-like receptor 4. J Immunol 168: 5233-5239.
40. Kaisho, T., Takeuchi, O., Kawai, T., Hoshino, K., and Akira, S. (2001) Endotoxin-induced maturation of MyD88-deficient dendritic cells. J Immunol 166: 5688-5694.
41. Kawai, T., Adachi, O., Ogawa, T., Takeda, K., and Akira, S. (1999) Unresponsiveness of MyD88-deficient mice to endotoxin. Immunity 11: 115-122.
42. Kawai, T., Takeuchi, O., Fujita, T., Inoue, J., Muhlradt, P.F., Sato, S., et al. (2001) Lipopolysaccharide stimulates the MyD88-independent pathway and results in activation of IRF-3 and the expression of a subset of LPS-inducible genes. J Immunol 167: 5887-5894.
43. Kawasaki, K., Akashi, S., Shimazu, R., Yoshida, T., Miyake, K., and Nishijima, M. (2000) Mouse Toll-like receptor 4-MD-2 complex mediates lipopolysaccharide-mimetic signal transduction by Taxol. J Biol Chem 275: 2251-2254.
44. Kobayashi, K., Hernandez, L.D., Galan, J.E., Janeway, C.A., Jr, Medzhitov, R., and Flavell, R.A. (2002a) IRAK-M is a negative regulator of Toll-like receptor signaling. Cell 110: 191-202.
45. Kobayashi, K., Inohara, N., Hernandez, L.D., Galan, J.E., Nunez, G., Janeway, C.A., et al. (2002b) RICK/Rip2/CARDIAK mediates signaling for receptors of the innate and adaptive immune systems. Nature 416: 194-199.
46. Krug, A., Rothenfusser, S., Hornung, V., Jahrsdorfer, B., Blackwell, S., Ballas, Z.K., et al. (2001) Identification of CpG oligonucleotide sequences with high induction of IFN-α/β in plasmacytoid dendritic cells. Eur J Immunol 31: 2154-2163.
47. Kurt-Jones, E.A., Popova, L., Kwinn, L., Haynes, L.M., Jones, L.P., Tripp, R.A., et al. (2000) Pattern recognition receptors TLR4 and CD14 meidate response to respiratory syncytial virus. Nat Immunol 1: 398-401.
48. Lemaitre, B., Kromer-Metzger, E., Michaut, L., Nicolas, E., Meister, M., Georgel, P., et al. (1995) A recessive mutation, immune deficiency (imd), defines two distinct control pathways in the Drosophila host defense. Proc Natl Acad Sci USA 92: 9465-9469.
49. Lemaitre, B., Nicolas, E., Michaut, L., Reichhart, J.-M., and Hoffmann, J.A. (1996) The dorsoventral regulatory gene cassette spatzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell 86: 973-983.
50. Li, S., Strelow, A., Fontana, E.J., and Wesche, H. (2002) IRAK-4, a novel member of the IRAK family with the properties of an IRAK-kinase. Proc Natl Acad Sci USA 99: 5567-5572.
51. Ligoxygakis, P., Pelte, N., Hoffmann, J.A., and Reichhart, J.M. (2002) Activation of Drosophila Toll during fungal infection by a blood serine protease. Science 297: 114-116.
52. Lomaga, M.A., Yeh, W.C., Sarosi, I., Duncan, G.S., Furlonger, C., Ho, A., et al. (1999) TRAF6 deficiency results in osteopetrosis and defective interleukin-1, CD40, and LPS signaling. Genes Dev 13: 1015-1024.
53. Medzhitov, R., Preston-Hurlburt, P., and Janeway, C.A., Jr (1997) A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 388: 394-397.
54. Medzhitov, R. (2001) Toll-like receptors and innate immunity. Nat Rev Immunol 1: 135-145.
55. Michel, T., Reichart, J.-M., Hoffmann, J.A., and Royet, J. (2001) Drosophila Toll activated by Gram-positive bacteria through a circulating peptidoglycan recognition protein. Nature 414: 756-759.
56. Nagai, Y., Akashi, S., Nagafuku, M., Ogata, M., Iwakura, Y., Akira, S., et al. (2002a) Essential role of MD-2 in LPS responsiveness and TLR4 distribution. Nat Immunol 3: 667-672.
57. Nagai, Y., Shimazu, R., Ogata, H., Akashi, S., Sudo, K., Yamasaki, H., et al. (2002b) Requirement for MD-1 in cell surface expression of RP105/CD180 and B-cell responsiveness to lipopolysaccharide. Blood 99: 1699-1705.
58. Naito, A., Azuma, S., Tanaka, S., Miyazaki, T., Takaki, S., Takatsu, K., et al. (1999) Severe osteopetrosis, defective interleukin-1 signalling and lymph node organogenesis in TRAF6-deficient mice. Genes Cells 4: 353-362.
59. O'Brien, A.D., Rosenstreich, D.L., Scher, I., Campbell, G.H., MacDermott, R.P., and Formal, S.B. (1980) Genetic control of susceptibility to Salmonella typhimurium. mice: role of the LPS gene. J Immunol 124: 20-24.
60. Ogata, H., Su, I., Miyake, K., Nagai, Y., Akashi, S., Mecklenbrauker, I., et al. (2000) The Toll-like receptor protein RP105 regulates lipopolysaccharide signaling in B cells. J Exp Med 192: 23-29.
61. Ohashi, K., Burkart, V., Flohe, S., and Kolb, H. (2000) Cutting edge: heat shock protein 60 is a putative endogenous ligand of the toll-like receptor-4 complex. J Immunol 164: 558-561.
62. Okamura, Y., Watari, M., Jerud, E.S., Young, D.W., Ishizaka, S.T., Rose, J., et al. (2001) The extra domain A of fibronectin activates Toll-like receptor 4. J Biol Chem 276: 10229-10233.
63. Ozinsky, A., Underhill, D.M., Fontenot, J.D., Hajjar, A.M., Smith, K.D., Wilson, C.B., et al. (2000) The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between Toll-like receptors. Proc Natl Acad Sci USA 97: 13766-13771.
64. Poltorak, A., He, X., Smirnova, I., Liu, M.Y., Du Huffel, C.V.X., Birdwell, D., et al. (1998) Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutation in Tlr4 gene. Science 282: 2085-2088.
65. Qureshi, S.T., Lariviere, L., Leveque, G., Clermont, S., Moore, K.J., Gros, P., and Malo, D. (1999) Endotoxin-tolerant mice have mutations in Toll-like receptor 4 (Tlr4). J Exp Med 189: 615-625.
66. Ramet, M., Manfruelli, P., Pearson, A., Mathey-Prevota, B., and Ezekowitz, A.B. (2002) Functional genomic analysis of phagocytosis and identification of a Drosophila receptor for E. coli. Nature 416: 644-648.
67. Rassa, J.C., Meyers, J.L., Zhang, Y., Kudaravalli, R., and Ross, S.R. (2002) Murine retroviruses activate B cells via interaction with Toll-like receptor 4. Proc Natl Acad Sci USA 99: 2281-2286.
68. Reiling, N., Holscher, C., Fehrenbach, A., Kroer, S., Kirschning, C.J., Goyert, S., and Ehlers, S. (2002) Cutting Edge: Toll-like receptor (TLR) 2- and TLR4-mediated pathogen recognition in resistance to airborne infection with Mycobacterium tuberculosis. J Immunol 169: 3480-3484.
69. Rock, F.L., Hardiman, G., Timans, J.C., Kastelein, R.A., and Bazan, J.F. (1998) A family of human receptors structurally related to Drosophila Toll. Proc Natl Acad Sci USA 95: 588-593.
70. Rutschmann, S., Kilinc, A., and Ferrandon, D. (2002) Cutting edge: The Toll pathway is required for resistance to Gram-positive bacterial infections in Drosophila. J Immunol 168: 1542-1546.
71. Sato, M., Suemori, H., Hata, N., Asagiri, M., Ogasawara, K., Nakao, K., et al. (2000) Distinct and essential roles of transcription factors IRF-3 and IRF-7 in response to viruses for IFN-α/β gene induction. Immunity 13: 539-548.
72. Schnare, M., Barton, G.M., Holt, A.C., Takeda, K., Akira, S., and Medzhitov, R. (2001) Toll-like receptors control activation of adaptive immune responses. Nat Immunol 2: 947-950.
73. Schromm, A.B., Lien, E., Henneke, P., Chow, J.C., Yoshimura, A., Heine, H., et al. (2001) Molecular genetic analysis of an endotoxin nonresponder mutant cell line: a point mutation in a conserved region of MD-2 abolishes endotoxin-induced signaling. J Exp Med 194: 79-88.
74. Seki, E., Tsutsui, H., Nakano, H., Tsuji, N., Hoshino, K., Adachi, O., et al, (2001) Lipopolysaccharide-induced IL-18 secretion from murine Kupffer cells independently of myeloid differentiation factor 88 that is critically involved in induction of production of IL-12 and IL-1β. J Immunol 166: 2651-2657.
75. Shimazu, R., Akashi, S., Ogata, H., Nagai, Y., Fukudome, K., Miyake, K., and Kimoto, M. (1999) MD-2, a molecule that confers lipopolysaccharide responsiveness on Toll-like receptor 4. J Exp Med 189: 1777-1782.
76. Smiley, S.T., King, J.A., and Hancock, W.W. (2001) Fibrinogen stimulates macrophage chemokine secretion through Toll-like receptor 4. J Immunol 167: 2887-2894.
77. Suzuki, N., Suzuki, S., Duncan, G.S., Millar, D.G., Wada, T., Mirtsos, C., et al. (2002) Severe impairment of interleukin-1 and Toll-like receptor signaling in mice lacking IRAK-4. Nature 416: 750-756.
78. Swantek, J.L., Tsen, M.F., Cobb, M.H., and Thomas, J.A. (2000) IL-1 receptor-associated kinase modulates host responsiveness to endotoxin. J Immunol 164: 4301-4306.
79. Takeuchi, O., Hoshino, K., Kawai, T., Sanjo, H., Takada, H., Ogawa, T., et al. (1999) Differential roles of TLR2 and TLR4 in recognition of Gram-negative and Gram-positive cell wall components. Immunity 11: 443-451.
80. Takeuchi, O., Kaufmann, A., Grote, K., Kawai, T., Hoshino, K., Morr, M., et al. (2000a) Cutting Edge: Preferentially the R-steroisomer of the Mycoplasmal lipopeptide macrophage-activating lipopeptide-2 activates immune cells through a Toll-like receptor 2- and MyD88-dependent signaling pathway. J Immunol 164: 554-557.
81. Takeuchi, O., Hoshino, K., and Akira, S. (2000b) Cutting edge: TLR2-deficient and MyD88-deficient mice are highly susceptible to Staphylococcus aureus infection. J Immunol 165: 5392-5396.
82. Takeuchi, O., Kawai, T., Muhlradt, P.F., Radolf, J.D., Zychlinsky, A., Takeda, K., and Akira, S. (2001) Discrimination of bacterial lipopeptides by Toll-like receptor 6. Int Immunol 13: 933-940.
83. Takeuchi, O., Horiuchi, T., Hoshino, K., Takeda, K., Dong, Z., Modlin, R.L., and Akira, S. (2002) Role of TLR1 in mediating immune response to microbial lipoproteins. J Immunol 169: 10-14.
84. Termeer, C., Benedix, F., Sleeman, J., Fieber, C., Voith, U., Ahrens, T., et al. (2002) Oligosaccharides of hyaluronan activate dendritic cells via Toll-like receptor 4. J Exp Med 195: 99-111.
85. Toshchakov, V., Jones, B.W., Perera, P.Y., Thomas, K., Cody, M.J., Zhang, S., et al. (2002) TLR4, but not TLR2, mediates IFN-β-induced STAT1α/β-dependent gene expression in macrophages. Nature Immunol 3: 392-398.
86. Underhill, D.M., and Ozinsky, A. (2002) Phagocytosis of microbes: complexity in action. Annu Rev Immunol 20: 825-852.
87. Vabulas, R.M., Ahmad-Nejad, P., da Costa, C., Miethke, T., Kirschning, C.J., Hacker, H., and Wagner, H. (2001) Endocytosed HSP60s use toll-like receptor 2 (TLR2) and TLR4 to activate the toll/interleukin-1 receptor signaling pathway in innate immune cells. J Biol Chem 276: 31332-31339.
88. Vabulas, R.M., Ahmad-Nejad, P., Ghose, S., Kirschning, C.J., Issels, R.D., and Wagner, H. (2002) HSP70 as endogenous stimulus of toll/interleukin-1 receptor signal pathway. J Biol Chem 277: 15107-15112.
89. Wagner, H. (1999) Bacterial CpG DNA activates immune cells to signal infectious danger. Adv Immunol 73: 329-367.
90. Weaver, B.K., Kumar, K.P., and Reich, N.C. (1998) Interferon regulatory factor 3 and CREB-binding protein/p300 are subunits of double-stranded RNA-activated transcription factor DRAF1. Mol Cell Biol 18: 1359-1368.
91. Werts, C., Tapping, R.I., Mathison, J.C., Chuang, T.-H., Kravchenko, V., Girons, I.S., et al. (2001) Leptospiral liopolysaccharide activates cells through a TLR2-dependent mechanism. Nat Immunol 2: 346-352.
92. Wesche, H., Gao, X., Li, X., Kirschning, C.J., Stark, G.R., and Cao, Z. (1999) IRAK-M is a novel member of the Pelle/interleukin-1 receptor-associated kinase (IRAK) family. J Biol Chem 274: 19403-19410.
93. Whitham, S., Dinesh-Kumar, S.P., Choi, D., Hehl, R., Corr, C., and Baker, B. (1994) The product of the tobacco mosaic virus resistance gene N: similarity to toll and the interleukin-1 receptor. Cell 78: 1101-1115.
94. Wooten, R.M., Ma, Y., Yoder, R.A., Brown, J.P., Weis, J.H., Zachary, J.F., et al. (2002) Toll-like receptor 2 is required for innate, but not acquired, host defense to Borrelia burgdorferi. J Immunol 168: 348-355.
95. Wurfel, M.M., Monks, B.G., Ingalls, R.R., Dedrick, R.L., Delude, R., Zhou, D., et al. (1997) Targeted deletion of the lipopolysaccharide (LPS)-binding protein gene leads to profound suppression of LPS responses ex vivo, whereas in vivo responses remain intact. J Exp Med 186: 2051-2056.
96. Yamamoto, M., Sato, S., Hemmi, H., Sanjo, H., Uematsu, S., Kaisho, T., et al. (2002) Essential role of TIRAP/Mal for activation of the signaling cascade shared by TLR2 and TLR4. Nature 420: 324-329.
97. 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 IRF-3 and CBP/p300. EMBO J 17: 1087-1095.