TLR signaling pathways: Opportunities for activation and blockade in pursuit of therapy

Current Pharmaceutical Design

Volumn 12, Issue 32, 2006, Pages 4123-4134

  Hoebe, K ^a   Jiang, Z ^a   Georgel, P ^a   Tabeta, K ^b   Janssen, E ^c   Du, X ^a   Beutler, Bruce ^a  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

^b NIIGATA UNIVERSITY GRADUATE SCHOOL OF MEDICAL AND DENTAL SCIENCES   (Japan)

^c LA JOLLA INSTITUTE FOR ALLERGY AND IMMUNOLOGY   (United States)

Author keywords

Microbial adjuvants; MyD88 dependent signal transduction; Sterile inflammation; TNF neutralization; Trif mutation

Indexed keywords

ADAPTOR PROTEIN; ANTIBIOTIC AGENT; B7 ANTIGEN; CD14 ANTIGEN; CD36 ANTIGEN; CD40 ANTIGEN; CD86 ANTIGEN; IMIDAZOQUINOLINE DERIVATIVE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERFERON REGULATORY FACTOR; INTERLEUKIN 1 RECEPTOR; INTERLEUKIN 18 RECEPTOR; LIPOPOLYSACCHARIDE; MYELOID DIFFERENTIATION FACTOR 88; PROTEIN MD 2; RECEPTOR BLOCKING AGENT; T LYMPHOCYTE RECEPTOR; TOLL LIKE RECEPTOR 1; TOLL LIKE RECEPTOR 10; TOLL LIKE RECEPTOR 2; TOLL LIKE RECEPTOR 3; TOLL LIKE RECEPTOR 4; TOLL LIKE RECEPTOR 5; TOLL LIKE RECEPTOR 6; TOLL LIKE RECEPTOR 7; TOLL LIKE RECEPTOR 8; TOLL LIKE RECEPTOR 9; TOLL LIKE RECEPTOR BLOCKING AGENT; TUMOR NECROSIS FACTOR; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ANTIGEN PRESENTATION; ANTINEOPLASTIC ACTIVITY; BACTERIAL INFECTION; BASAL CELL CARCINOMA; DRUG RESEARCH; DRUG TARGETING; GENETIC ANALYSIS; GRAM NEGATIVE BACTERIUM; HUMAN; IMMUNE RESPONSE; INFECTION RESISTANCE; INFLAMMATION; INNATE IMMUNITY; MALIGNANT NEOPLASTIC DISEASE; MAMMAL; MOLECULAR CLONING; NONHUMAN; PAPILLOMA; PRIORITY JOURNAL; RECEPTOR BLOCKING; RECEPTOR UPREGULATION; REVIEW; SIGNAL TRANSDUCTION;

ANTI-INFLAMMATORY AGENTS; BACTERIAL INFECTIONS; SIGNAL TRANSDUCTION; TOLL-LIKE RECEPTORS;

EID: 33750574752     PISSN: 13816128     EISSN: None     Source Type: Journal    
DOI: 10.2174/138161206778743466     Document Type: Review

References (109)

1. Elliott MJ, Maini RN, Feldmann M, Kalden JR, Antoni C, Smolen, JS, et al. Randomised double-blind comparison of chimeric monoclonal antibody to tumour necrosis factor α (cA2) versus placebo in rheumatoid arthritis. Lancet 1994; 344: 1105-1110.
2. Brandt J, Haibel H, Cornely D, Golder W, Gonzalez J, Reddig J, et al. Successful treatment of active ankylosing spondylitis with the anti- tumor necrosis factor alpha monoclonal antibody infliximab. Arthritis Rheum 2000; 43: 1346-1352.
3. Beutler B, Mahoney J, Le Trang N, Pekala P, Cerami A. Purification of cachectin, a lipoprotein lipase-suppressing hormone secreted by endotoxin-induced RAW 264.7 cells. J Exp Med 1985; 161: 984-995.
4. Beutler B, Greenwald D, Hulmes JD, Chang M, Pan Y-CE, Mathison J, et al. Identity of tumour necrosis factor and the macrophage-secreted factor cachectin. Nature 1985; 316: 552-554.
5. Beutler B, Milsark IW, Cerami A. Passive immunization against cachectin/ tumor necrosis factor (TNF) protects mice from the lethal effect of endotoxin. Science 1985; 229: 869-871.
6. Havell EA. Evidence that tumor necrosis factor has an important role in antibacterial resistance. J Immunol 1989; 143: 2894-2899.
7. Kindler V, Sappino A-P, Grau GE, Piguet P-F, Vassalli P. The inducing role of tumor necrosis factor in the development of bactericidal granulomas during BCG infection. Cell 1989; 56: 731-740.
8. Michalek SM, Moore RN, McGhee JR, Rosenstreich DL, Mergenhagen SE. The primary role of lymphoreticular cells in the mediation of host responses to bacterial endotoxin. J Infect Dis 1980; 141: 55-63.
9. O'Brien AD, Rosenstreich DL, Scher I, Campbell GH, MacDermott RP, Formal SB. Genetic control of susceptibility to Salmonella typhimurium in mice: role of the LPS gene. J. Immunol 1980; 124: 20-24.
10. Rosenstreich DL, Weinblatt AC, O'Brien AD. Genetic control of resistance to infection in mice. CRC Crit Rev Immunol 1982; 3: 263-330.
11. Hagberg L, Hull R, Hull S, McGhee JR, Michalek SM, Svanborg Eden C. Difference in susceptibility to gram-negative urinary tract infection between C3H/HeJ and C3H/HeN mice. Infect Immun 1984; 46: 839-844.
12. Wright SD, Ramos RA, Tobias PS, Ulevitch RJ, Mathison JC. CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein. Science 1990; 249: 1431-1433.
13. Ferrero E, Jiao D, Tsuberi BZ, Tesio L, Rong GW, Haziot A, et al. Transgenic mice expressing human CD14 are hypersensitive to lipopolysaccharide. Proc Natl Acad Sci USA 1993; 90: 2380-2384.
14. Haziot A, Ferrero E, Kontgen F, Hijiya N, Yamamoto S, Silver J, et al. Resistance to endotoxin shock and reduced dissemination of gram-negative bacteria in CD14-deficient mice. Immunity 1996; 4: 407-414.
15. Ulevitch RJ. Recognition of bacterial endotoxins by receptor-dependent mechanisms. Adv Immunol 1993; 53: 267-289.
16. Heppner G, Weiss DW. High susceptibility of strain A mice to endotoxin and endotoxin-red blood cell mixtures. J Bacteriol 1965; 90: 696-703.
17. Watson J, Riblet R. Genetic control of responses to bacterial lipopolysaccharides in mice. II. A gene that influences a membrane component involved in the activation of bone marrow-derived lymphocytes by lipipolysaccharides. J Immunol 1975; 114: 1462-1468.
18. Watson J, Riblet R, Taylor BA. The response of recombinant inbred strains of mice to bacterial lipopolysaccharides. J Immunol 1977; 118: 2088-2093.
19. Watson J, Kelly K, Largen M, Taylor BA. The genetic mapping of a defective LPS response gene in C3H/HeJ mice. J Immunol 1978; 120: 422-424.
20. Coutinho A, Meo T. Genetic basis for unresponsiveness to lipopolysaccharide in C57BL/10Cr mice. Immunogenetics 1978; 7: 17-24.
21. Coutinho A, Forni L, Melchers F, Watanabe T. Genetic defect in responsiveness to the B cell mitogen lipopolysaccharide. Eur J Immunol 1977; 7: 325-328.
22. Poltorak A, He X, Smirnova I, Liu M-Y, Van Huffel C, Du X, et al. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 1998; 282: 2085-2088.
23. Poltorak, A, Smirnova, I, Clisch, R, Beutler, B. Limits of a deletion spanning Tlr4 in C57BL/10ScCr mice. J Endotoxin Res 2000; 6: 51-56.
24. Poltorak A, Ricciardi-Castagnoli P, Citterio A, Beutler B. Physical contact between LPS and Tlr4 revealed by genetic complementation. Proc Natl Acad Sci USA 2000; 97: 2163-2167.
25. Lien E, Means TK, Heine H, Yoshimura A, Kusumoto S, Fukase, K, et al. Toll-like receptor 4 imparts ligand-specific recognition of bacterial lipopolysaccharide. J Clin Invest 2000; 105: 497-504.
26. Jude BA, Pobezinskaya Y, Bishop J, Parke S, Medzhitov RM, Chervonsky AV, et al. Subversion of the innate immune system by a retrovirus. Nat Immunol 2003; 4: 573-578.
27. Hoebe K, Du X, Georgel P, Janssen E, Tabeta K, Kim SO, et al. Identification of Lps2 as a key transducer of MyD88-independent TIR signaling. Nature 2003; 424: 743-748.
28. Yamamoto M, Sato S, Hemmi H, Hoshino K, Kaisho T, Sanjo H, et al. Role of adapter TRIF in the MyD88-independent Toll-like receptor signaling pathway. Science 2003, 301: 640-643.
29. Beutler B, Du X, Hoebe K. From phenomenon to phenotype and from phenotype to gene: forward genetics and the problem of sepsis. J Infect Dis 2003; 187(Suppl 2): S321-S326.
30. Shimazu R, Akashi S, Ogata H, Nagai Y, Fukudome K, Miyake K, et al. MD-2, a molecule that confers lipopolysaccharide responsiveness on Toll-like receptor 4. J Exp Med 1999; 189: 1777-1782.
31. Nagai Y, Akashi S, Nagafuku M, Ogata M, Iwakura Y, Akira S, et al. Essential role of MD-2 in LPS responsiveness and TLR4 distribution. Nat Immunol 2002; 3: 667-672.
32. Fitzgerald KA, Palsson-McDermott EM, Bowie AG, Jefferies CA, Mansell AS, Brady G, et al. Mal (MyD88-adapter-like) is required for Toll-like receptor-4 signal transduction. Nature 2001; 413: 78-83.
33. Horng T, Barton GM, Medzhitov R. TIRAP: an adapter molecule in the Toll signaling pathway. Nat Immunol 2001; 2: 835-841.
34. Yamamoto M, Sato S, Hemmi H, Sanjo H, Uematsu S, Kaisho T, et al. Essential role for TIRAP in activation of the signalling cascade shared by TLR2 and TLR42. Nature 2002; 420: 324-329.
35. Horng T, Barton GM, Flavell RA, Medzhitov R. The adaptor molecule TIRAP provides signalling specificity for Toll-like receptors 1. Nature 2002; 420: 329-333.
36. Kawai T, Takeuchi O, Fujita T, Inoue J, Muhlradt PF, Sato S, 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 2001; 167: 5887-5894.
37. Oshiumi H, Matsumoto M, Funami K, Akazawa T, Seya T. TICAM-1, an adaptor molecule that participates in Toll-like receptor 3-mediated interferon-beta induction. Nat Immunol 2003; 4: 161-171.
38. Sato S, Sugiyama M, Yamamoto M, Watanabe Y, Kawai T, Takeda K, et al. Toll/IL-1 receptor domain-containing adaptor inducing IFN-beta (TRIF) associates with TNF receptor-associated factor 6 and TANK-binding kinase 1, and activates two distinct transcription factors, NF-kappa B and IFN-regulatory factor-3, in the Toll-like receptor signaling. J Immunol 2003; 171: 4304-4310.
39. Yamamoto M, Sato S, Hemmi H, Uematsu S, Hoshino K Kaisho, et al. TRAM is specifically involved in the Toll-like receptor 4-mediated MyD88-independent signaling pathway. Nat Immunol 2003; 4: 1144-1150.
40. Oshiumi H, Sasai M, Shida K, Fujita T, Matsumoto M, Seya T. TIR-containing adapter molecule (TICAM)-2, a bridging adapter recruiting to toll-like receptor 4 TICAM-1 that induces interferon-beta. J Biol Chem 2003; 278: 49751-49762.
41. Car BD, Eng VM, Schnyder B, Ozmen L, Huang S, Gallay P, et al. Interferon gamma receptor deficient mice are resistant to endotoxic shock. J Exp Med 1994; 179: 1437-1444.
42. Ozmen L, Pericin M, Hakimi J, Chizzonite RA, Wysocka M, Trinchieri G, et al. Interleukin 12, interferon gamma, and tumor necrosis factor α are the key cytokines of the generalized Shwartzman reaction. J Exp Med 1994: 180: 907-915.
43. Wysocka M, Kubin M, Vieira LQ, Ozmen L, Garotta G, Scott, P, et al. Interleukin-12 is required for interferon-gamma production and lethality in lipopolysaccharide-induced shock in mice. Eur J Immunol 1995; 25: 672-676.
44. Karaghiosoff M, Steinborn R, Kovarik P, Kriegshauser G, Baccarini M, Donabauer B, et al. Central role for type I interferons and Tyk2 in lipopolysaccharide-induced endotoxin shock. Nat Immunol 2003; 4: 471-477.
45. Jiang Z, Georgel P, Du X, Shamel L, Sovath S, Mudd S, et al. CD14 is required for MyD88-independent LPS signaling. Nat Immunol 2005; 6: 565-570.
46. Ozinsky A, Underhill DM, Fontenot JD, Hajjar AM, Smith KD, Wilson CB, et al. 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 2000; 97: 13766-13771.
47. Stanger BZ, Leder P, Lee T-H, Kim E, Seed B. RIP: A novel protein containing a death domain that interacts with Fas/Apo-1 (CD95) in yeast and causes cell death. Cell 1995; 81: 513-523.
48. Meylan E, Burns K, Hofmann K, Blancheteau V, Martinon F, Kelliher M, et al. RIP1 is an essential mediator of Toll-like receptor 3-induced NF-kappa B activation. Nat Immunol 2004; 5: 503-507.
49. Hoebe K, Georgel P, Rutschmann S, Du X, Mudd S, Crozat K, et al. CD36 is a sensor of diacylglycerides. Nature 2005, 433: 523-527.
50. Takeuchi O, Sato S, Horiuchi T, Hoshino K, Takeda K, Dong Z, et al. Cutting edge: role of Toll-like receptor 1 in mediating immune response to microbial lipoproteins. J Immunol 2002; 169: 10-14.
51. Buwitt-Beckmann U, Heine H, Wiesmuller KH, Jung G, Brock R, Akira S, et al. Toll-like receptor 6-independent signaling by diacylated lipopeptides. Eur J Immunol 2005; 35: 282-289.
52. Endemann G, Stanton LW, Madden KS, Bryant CM, White RT, Protter AA. CD36 is a receptor for oxidized low density lipoprotein 2. J Biol Chem 1993; 268: 11811-11816.
53. Janssen E, Tabeta K, Barnes M, McBride S, Schoenberger S, Theofilopoulos AN, et al. A cell death-induced, TLR-independent pathway drives efficient T cell activation. Immunity 2006; in press.
54. Schroder NW, Morath S, Alexander C, Hamann L, Hartung T, Zahringer U, et al. Lipoteichoic acid (LTA) of Streptococcus pneumoniae and Staphylococcus aureus activates immune cells via Toll-like receptor (TLR)-2, lipopolysaccharide-binding protein (LBP), and CD14, whereas TLR-4 and MD-2 are not involved. J Biol Chem 2003; 278: 15587-15594.
55. Condie RM, Zak SJ, Good RA. Effect of meningococcal endotoxin on the immune response. Proc Soc Exp Biol Med 1955; 90: 355-360.
56. Azuma M, Cayabyab M, Buck D, Phillips JH, Lanier LL. CD28 interaction with B7 costimulates primary allogeneic proliferative responses and cytotoxicity mediated by small, resting T lymphocytes. J Exp Med 1992; 175: 353-360.
57. Chen L, Ashe S, Brady WA, Hellstrom I, Hellstrom KE, Ledbetter, JA, et al. Costimulation of antitumor immunity by the B7 counter-receptor for the T lymphocyte molecules CD28 and CTLA-4. Cell 1992; 71: 1093-1102.
58. De Boer M, Kasran A, Kwekkeboom J, Walter H, Vandenberghe P, Ceuppens JL. Ligation of B7 with CD28/CTLA-4 on T cells results in CD40 ligand expression, interleukin-4 secretion and efficient help for antibody production by B cells. Eur J Immunol 1993; 23: 3120-3125.
59. Green JM, Noel PJ, Sperling AI, Walunas TL, Gray GS, Bluestone JA, et al. Absence of B7-dependent responses in CD28-deficient mice. Immunity 1994; 1: 501-508.
60. Medzhitov R, Preston-Hurlburt P, Janeway CA. A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 1997; 388: 394-397.
61. Kaisho T, Takeuchi O, Kawai T, Hoshino K, Akira S. Endotoxin-induced maturation of myd88-deficient dendritic cells. J Immunol 2001; 166: 5688-5694.
62. Kaisho T, Akira S. Dendritic-cell function in Toll-like receptor- and MyD88-knockout mice. Trends Immunol 2001; 22: 78-83.
63. Hoebe K, Jannsen EM, Kim SO, Alexopoulou L, Flavell RA, Han, J, et al. Upregulation of costimulatory molecules induced by lipopolysaccharide and double-stranded RNA occurs by Trif-dependent and Trif-independent pathways. Nature Immunology 2003; 4: 1223-1229.
64. Le Bon A, Schiavoni G, D'Agostino G, Gresser I, Belardelli F, Tough DF. Type i interferons potently enhance humoral immunity and can promote isotype switching by stimulating dendritic cells in vivo. Immunity 2001; 14: 461-470.
65. Le Bon A, Tough, DF. Links between innate and adaptive immunity via type I interferon. Curr Opin Immunol 2002; 14: 432-436.
66. Yoneyama M, Kikuchi M, Natsukawa T, Shinobu N, Imaizumi T, Miyagishi M, et al. The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nat Immunol 2004; 5: 730-737.
67. Yoneyama M, Kikuchi M, Matsumoto K, Imaizumi T, Miyagishi M, Taira K, et al. Shared and unique functions of the DExD/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity. J Immunol 2005; 175: 2851-2858.
68. Kawai T, Takahashi K, Sato S, Coban C, Kumar H, Kato H, et al. IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction. Nat Immunol 2005; 6: 981-988.
69. Kawai T, Adachi O, Ogawa T, Takeda K, Akira S. Unresponsiveness of MyD88-deficient mice to endotoxin. Immunity 1999; 11: 115-122.
70. Jiang Z, Mak TW, Sen G, Li X. Toll-like receptor 3-mediated activation of NF-kappaB and IRF3 diverges at Toll-IL-1 receptor domain-containing adapter inducing IFN-beta. Proc Natl Acad Sci USA 2004; 101: 3533-3538.
71. Janeway CA Jr. Approaching the asymptote? Evolution and revolution in immunology 20. Cold Spring Harb Symp Quant Biol 1989; 54 Pt 1: 1-13.
72. Tabeta K, Hoebe K, Jannsen EM, Georgel P, Crozat K, Mudd S, et al. 3d, a missense mutation that disrupts exogenous antigen presentation and signaling via Toll-like receptors 3, 7, and 9. Nat Immunol 2006; 7: 156-164.
73. de la Cruz I, Levin JZ, Cummins C, Anderson P, Horvitz HR. sup-9, sup-10, and unc-93 may encode components of a two-pore K+ channel that coordinates muscle contraction in Caenorhabditis elegans. J Neurosci 2003; 23: 9133-9145.
74. Hacker H, Mischak H, Miethke T, Liptay S, Schmid R, Sparwasser T, et al. CpG-DNA-specific activation of antigen-presenting cells requires stress kinase activity and is preceded by non-specific endocytosis and endosomal maturation. EMBO J 1998; 17: 6230-6240.
75. MacFarlane DE, Manzel L. Antagonism of immunostimulatory CpGr-oligodeoxynucleotides by quinacrine, chloroquine, and structurally related compounds. J Immunol 1998; 160: 1122-1131.
76. Rutz M, Metzger J, Gellert T, Luppa P, Lipford GB, Wagner H, et al. Toll-like receptor 9 binds single-stranded CpG-DNA in a sequence- and pH-dependent manner. Ent J Immunol 2004; 34: 2541-2550.
77. Sioud M. Induction of inflammatory cytokines and interferon responses by double-stranded and single-stranded siRNAs is sequence-dependent and requires endosomal localization. J Mol Biol 2005; 348: 1079-1090.
78. Lund JM, Alexopoulou L, Sato A, Karow M, Adams NC, Gale NW, et al. Recognition of single-stranded RNA viruses by Toll-like receptor 7. Proc Natl Acad Sci USA 2004; 101: 5598-5603.
79. Lee J, Chuang TH, Redecke V, She L, Pitha PM, Carson DA, et al. Molecular basis for the immunostimulatory activity of guanine nucleoside analogs: activation of Toll-like receptor 7. Proc Natl Acad Sci USA 2003; 100: 6646-6651.
80. de Bouteiller O, Merck E, Hasan UA, Hubac S, Benguigui B, Trinchieri G, et al. Recognition of double stranded RNA by human toll like receptor 3 and downstream receptor signaling requires multimerisation and an acidic pH. J Biol Chem 2005; 280: 38133-38145.
81. Gagnon E, Duclos S, Rondeau C, Chevet E, Cameron PH, Steele-Mortimer O, et al. Endoplasmic reticulum-mediated phagocytosis is a mechanism of entry into macrophages. Cell 2002; 110: 119-131.
82. Guermonprez P, Saveanu L, Kleijmeer M, Davoust J, van EP, Amigorena S. ER-phagosome fusion defines an MHC class I cross-presentation compartment in dendritic cells. Nature 2003; 425: 397-402.
83. Touret N, Paroutis P, Grinstein S. The nature of the phagosomal membrane: endoplasmic reticulum versus plasmalemma. J Leukoc Biol 2005; 77: 878-885.
84. Croker JA, Kimberly RP. SLE: challenges and candidates in human disease. Trends Immunol 2005; 26: 580-586.
85. Liu CC, Manzi S, Ahearn JM. Biomarkers for systemic lupus erythematosus: a review and perspective. Curr Opin Rheumatol 2005; 17: 543-549.
86. Kirou KA, Lee C, George S, Louca K, Papagiannis IG, Peterson MG, et al. Coordinate overexpression of interferon-alpha-induced genes in systemic lupus erythematosus. Arthritis Rheum 2004; 50: 3958-3967.
87. Baechler EC, Gregersen PK, Behrens TW. The emerging role of interferon in human systemic lupus erythematosus. Curr Opin Immunol 2004; 16: 801-807.
88. Crow MK, Kirou KA, Wohlgemuth J. Microarray analysis of interferon-regulated genes in SLE. Autoimmunity 2003; 36: 481-490.
89. Pascual V, Banchereau J, Palucka AK. The central role of dendritic cells and interferon-alpha in SLE. Curr Opin Rheumatol 2003; 15: 548-556.
90. Bennett L, Palucka AK, Arce E, Cantrell V, Borvak J, Banchereau J, et al. Interferon and granulopoiesis signatures in systemic lupus erythematosus blood. J Exp Med 2003; 197: 711-723.
91. Baechler EC, Batliwalla FM, Karypis G, Gaffney PM, Ortmann WA, Espe KJ, et al. Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus. Proc Natl Acad Sci USA 2003; 100: 2610-2615.
92. Leadbetter EA, Rifkin IR, Hohlbaum AM, Beaudette BC, Shlomchik MJ, Marshak-Rothstein A. Chromatin-IgG complexes activate B cells by dual engagement of IgM and Toll-like receptors. Nature 2002; 416: 603-607.
93. Viglianti GA, Lau CM, Hanley TM, Miko BA, Shlomchik MJ, Marshak-Rothstein A. Activation of autoreactive B cells by CpG dsDNA. Immunity 2003; 19: 837-847.
94. Christensen SR, Kashgarian M, Alexopoulou L, Flavell RA, Akira S, Shlomchik MJ. Toll-like receptor 9 controls anti-DNA autoantibody production in murine lupus. J Exp Med 2005; 202: 321-331.
95. Hoffman RW, Gazitt T, Foecking MF, Ortmann RA, Misfeldt M, Jorgenson R, et al. U1 RNA induces innate immunity signaling. Arthritis Rheum 2004; 50: 2891-2896.
96. Termeer C, Benedix F, Sleeman J, Fieber C, Voith U, Ahrens T, et al. Oligosaccharides of Hyaluronan activate dendritic cells via toll-like receptor 4. J Exp Med 2002; 195: 99-111.
97. Takayama K, Qureshi N, Beutler B, Kirkland TN. Diphosphoryl lipid A from Rhodopseudomonas spaeroides ATCC 17023 blocks induction of cachectin in macrophages by lipopolysaccharide. Infect Immun 1989; 57: 1336-1338.
98. Christ WJ, Asano O, Robidoux AL, Perez M, Wang Y, Dubuc GR, et al. E5531, a pure endotoxin antagonist of high potency. Science 1995; 268: 80-83.
99. Jiang D, Liang J, Fan J, Yu S, Chen S, Luo Y, et al. Regulation of lung injury and repair by Toll-like receptors and hyaluronan. Nat Med 2005; 11:1173-1179.
100. Zhang X, Shan P, Qureshi S, Homer R, Medzhitov R, Noble PW, et al. Cutting Edge: TLR4 Deficiency Confers Susceptibility to Lethal Oxidant Lung Injury. J Immunol 2005; 175: 4834-4838.
101. Bartfai T, Behrens MM, Gaidarova S, Pemberton J, Shivanyuk A, Rebek J Jr. A low molecular weight mimic of the Toll/IL-1 receptor/resistance domain inhibits IL-1 receptor-mediated responses. Proc Natl Acad Sci USA 2003; 100: 7971-7976.
102. Tighe H, Takabayashi K, Schwartz D, Marsden R, Beck L, Corbeil J, et al. Conjugation of protein to immunostimulatory DNA results in a rapid, long-lasting and potent induction of cell-mediated and humoral immunity. Eur J Immunol 2000; 30: 1939-1947.
103. Hawkins LD, Ishizaka ST, McGuinness P, Zhang H, Gavin W, DeCosta B, et al. A novel class of endotoxin receptor agonists with simplified structure, toll-like receptor 4-dependent immunostimulatory action, and adjuvant activity. J Pharmacol Exp Ther 2002; 300: 655-661.
104. Persing DH, Coler RN, Lacy MJ, Johnson DA, Baldridge JR, Hershberg RM, et al. Taking toll: lipid A mimetics as adjuvants and immunomodulators. Trends Microbiol 2002; 10: S32-S37.
105. Wille-Reece U, Flynn BJ, Lore K, Koup RA, Kedl RM, Mattapallil JJ, et al. HIV Gag protein conjugated to a Toll-like receptor 7/8 agonist improves the magnitude and quality of Th1 and CD8+ T cell responses in nonhuman primates. Proc Natl Acad Sci USA 2005; 102: 15190-15194.
106. Inohara N, Chamaillard M, McDonald C, Nunez G. NOD-LRR Proteins: Role in Host-Microbial Interactions and Inflammatory Disease. Annu Rev Biochem 2005; 74: 355-383.
107. Furnkranz A, Leitinger N. Regulation of inflammatory responses by oxidized phospholipids: structure-function relationships. Curr Pharm Des 2004; 10(8): 915-21.
108. Hiemstra PS, Fernie-King BA, McMichael J, Lachmann PJ, Sallenave JM. Antimicrobial peptides: mediators of innate immunity as templates for the development of novel anti-infective and immune therapeutics. Curr Pharm Des 2004; 10(23): 2891-905.
109. Kusnecov AW, Goldfarb Y. Neural and behavioral responses to systemic immunologic stimuli: a consideration of bacterial T cell superantigens. Curr Pharm Des 2005; 11(8): 1039-46.