TLRs and chronic inflammation

International Journal of Biochemistry and Cell Biology

Volumn 42, Issue 4, 2010, Pages 495-505

  Ospelt, Caroline ^a   Gay, Steffen ^a  

^a UNIVERSITY HOSPITAL ZURICH   (Switzerland)

Author keywords

Chronic inflammation; Innate immunity; TLRs

Indexed keywords

CATHEPSIN K INHIBITOR; CHAPERONIN; HEAT SHOCK PROTEIN 60; HISTONE DEACETYLASE; HYDROXYCHLOROQUINE; TOLL LIKE 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 AGONIST;

ALLERGY; CHRONIC INFLAMMATION; DIABETES MELLITUS; DRUG RECEPTOR BINDING; ENTERITIS; HUMAN; IMMUNOPATHOGENESIS; IMMUNOSTIMULATION; INNATE IMMUNITY; LYMPHOCYTE ACTIVATION; MOLECULAR BIOLOGY; NERVOUS SYSTEM INFLAMMATION; NONHUMAN; PROTEIN EXPRESSION; PROTEIN SYNTHESIS INHIBITION; PSORIASIS; REVIEW; RHEUMATOID ARTHRITIS; SEPSIS; SIGNAL TRANSDUCTION; SYSTEMIC LUPUS ERYTHEMATOSUS;

ANIMALS; AUTOIMMUNE DISEASES; CHRONIC DISEASE; HUMANS; IMMUNITY, INNATE; INFLAMMATION; SIGNAL TRANSDUCTION; TOLL-LIKE RECEPTORS;

EID: 77649180575     PISSN: 13572725     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.biocel.2009.10.010     Document Type: Review

References (162)

1. Abdollahi-Roodsaz S., Joosten L.A., Koenders M.I., Devesa I., Roelofs M.F., Radstake T.R., et al. Stimulation of TLR2 and TLR4 differentially skews the balance of T cells in a mouse model of arthritis. J Clin Invest 118 1 (2008) 205-216
2. Alexopoulou L., Holt A.C., Medzhitov R., and Flavell R.A. Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature 413 6857 (2001) 732-738
3. Alexopoulou L., Thomas V., Schnare M., Lobet Y., Anguita J., Schoen R.T., et al. Hyporesponsiveness to vaccination with Borrelia burgdorferi OspA in humans and in TLR1- and TLR2-deficient mice. Nat Med 8 8 (2002) 878-884
4. Anderson K.V., Bokla L., and Nusslein-Volhard C. Establishment of dorsal-ventral polarity in the Drosophila embryo: the induction of polarity by the Toll gene product. Cell 42 3 (1985) 791-798
5. Anderson K.V., Jurgens G., and Nusslein-Volhard C. Establishment of dorsal-ventral polarity in the Drosophila embryo: genetic studies on the role of the Toll gene product. Cell 42 3 (1985) 779-789
6. Asagiri M., Hirai T., Kunigami T., Kamano S., Gober H.J., Okamoto K., et al. Cathepsin K-dependent toll-like receptor 9 signaling revealed in experimental arthritis. Science 319 5863 (2008) 624-627
7. Asea A., Rehli M., Kabingu E., Boch J.A., Bare O., Auron P.E., et al. Novel signal transduction pathway utilized by extracellular HSP70: role of toll-like receptor (TLR) 2 and TLR4. J Biol Chem 277 17 (2002) 15028-15034
8. Aung H.T., Schroder K., Himes S.R., Brion K., van Zuylen W., Trieu A., et al. LPS regulates proinflammatory gene expression in macrophages by altering histone deacetylase expression. FASEB J 20 9 (2006) 1315-1327
9. Baker B.S., Ovigne J.M., Powles A.V., Corcoran S., and Fry L. Normal keratinocytes express Toll-like receptors (TLRs) 1, 2 and 5: modulation of TLR expression in chronic plaque psoriasis. Br J Dermatol 148 4 (2003) 670-679
10. Barrat F.J., Meeker T., Chan J.H., Guiducci C., and Coffman R.L. Treatment of lupus-prone mice with a dual inhibitor of TLR7 and TLR9 leads to reduction of autoantibody production and amelioration of disease symptoms. Eur J Immunol 37 12 (2007) 3582-3586
11. Bausinger H., Lipsker D., Ziylan U., Manie S., Briand J.P., Cazenave J.P., et al. Endotoxin-free heat-shock protein 70 fails to induce APC activation. Eur J Immunol 32 12 (2002) 3708-3713
12. Bell J.K., Mullen G.E., Leifer C.A., Mazzoni A., Davies D.R., and Segal D.M. Leucine-rich repeats and pathogen recognition in Toll-like receptors. Trends Immunol 24 10 (2003) 528-533
13. Bell J.K., Botos I., Hall P.R., Askins J., Shiloach J., Segal D.M., et al. The molecular structure of the Toll-like receptor 3 ligand-binding domain. Proc Natl Acad Sci USA 102 31 (2005) 10976-10980
14. Bode K.A., Schroder K., Hume D.A., Ravasi T., Heeg K., Sweet M.J., et al. Histone deacetylase inhibitors decrease Toll-like receptor-mediated activation of proinflammatory gene expression by impairing transcription factor recruitment. Immunology 122 4 (2007) 596-606
15. Bowie A., Kiss-Toth E., Symons J.A., Smith G.L., Dower S.K., and O'Neill L.A. A46R and A52R from vaccinia virus are antagonists of host IL-1 and toll-like receptor signaling. Proc Natl Acad Sci USA 97 18 (2000) 10162-10167
16. Boyd J.H., Mathur S., Wang Y., Bateman R.M., and Walley K.R. Toll-like receptor stimulation in cardiomyoctes decreases contractility and initiates an NF-kappaB dependent inflammatory response. Cardiovasc Res 72 3 (2006) 384-393
17. Brentano F., Schorr O., Gay R.E., Gay S., and Kyburz D. RNA released from necrotic synovial fluid cells activates rheumatoid arthritis synovial fibroblasts via Toll-like receptor 3. Arthritis Rheum 52 9 (2005) 2656-2665
18. Brown G.D., Herre J., Williams D.L., Willment J.A., Marshall A.S., and Gordon S. Dectin-1 mediates the biological effects of beta-glucans. J Exp Med 197 9 (2003) 1119-1124
19. Browning B.L., Huebner C., Petermann I., Gearry R.B., Barclay M.L., Shelling A.N., et al. Has toll-like receptor 4 been prematurely dismissed as an inflammatory bowel disease gene? Association study combined with meta-analysis shows strong evidence for association. Am J Gastroenterol 102 11 (2007) 2504-2512
20. Bsibsi M., Ravid R., Gveric D., and van Noort J.M. Broad expression of Toll-like receptors in the human central nervous system. J Neuropathol Exp Neurol 61 11 (2002) 1013-1021
21. Campos M.A., Almeida I.C., Takeuchi O., Akira S., Valente E.P., Procopio D.O., et al. Activation of Toll-like receptor-2 by glycosylphosphatidylinositol anchors from a protozoan parasite. J Immunol 167 1 (2001) 416-423
22. Cao W., Bao C., Padalko E., and Lowenstein C.J. Acetylation of mitogen-activated protein kinase phosphatase-1 inhibits Toll-like receptor signaling. J Exp Med 205 6 (2008) 1491-1503
23. Cario E., and 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 12 (2000) 7010-7017
24. Cario E., Gerken G., and Podolsky D.K. Toll-like receptor 2 enhances ZO-1-associated intestinal epithelial barrier integrity via protein kinase C. Gastroenterology 127 1 (2004) 224-238
25. Chi H., Barry S.P., Roth R.J., Wu J.J., Jones E.A., Bennett A.M., et al. Dynamic regulation of pro- and anti-inflammatory cytokines by MAPK phosphatase 1 (MKP-1) in innate immune responses. Proc Natl Acad Sci USA 103 7 (2006) 2274-2279
26. Choe J., Kelker M.S., and Wilson I.A. Crystal structure of human toll-like receptor 3 (TLR3) ectodomain. Science 309 5734 (2005) 581-585
27. Cirl C., Wieser A., Yadav M., Duerr S., Schubert S., Fischer H., et al. Subversion of Toll-like receptor signaling by a unique family of bacterial Toll/interleukin-1 receptor domain-containing proteins. Nat Med 14 4 (2008) 399-406
28. Compton T., Kurt-Jones E.A., Boehme K.W., Belko J., Latz E., Golenbock D.T., et al. Human cytomegalovirus activates inflammatory cytokine responses via CD14 and Toll-like receptor 2. J Virol 77 8 (2003) 4588-4596
29. Deng G.M., Nilsson I.M., Verdrengh M., Collins L.V., and Tarkowski A. Intra-articularly localized bacterial DNA containing CpG motifs induces arthritis. Nat Med 5 6 (1999) 702-705
30. Dogusan Z., Garcia M., Flamez D., Alexopoulou L., Goldman M., Gysemans C., et al. Double-stranded RNA induces pancreatic beta-cell apoptosis by activation of the toll-like receptor 3 and interferon regulatory factor 3 pathways. Diabetes 57 5 (2008) 1236-1245
31. Dybdahl B., Wahba A., Lien E., Flo T.H., Waage A., Qureshi N., et al. Inflammatory response after open heart surgery: release of heat-shock protein 70 and signaling through toll-like receptor-4. Circulation 105 6 (2002) 685-690
32. Edelmann K.H., Richardson-Burns S., Alexopoulou L., Tyler K.L., Flavell R.A., and Oldstone M.B. Does Toll-like receptor 3 play a biological role in virus infections?. Virology 322 2 (2004) 231-238
33. Fanti P.A., Dika E., Vaccari S., Miscial C., and Varotti C. Generalized psoriasis induced by topical treatment of actinic keratosis with imiquimod. Int J Dermatol 45 12 (2006) 1464-1465
34. Fitzner N., Clauberg S., Essmann F., Liebmann J., and Kolb-Bachofen V. Human skin endothelial cells can express all 10 TLR genes and respond to respective ligands. Clin Vaccine Immunol 15 1 (2008) 138-146
35. Forsbach A., Nemorin J.G., Montino C., Muller C., Samulowitz U., Vicari A.P., et al. Identification of RNA sequence motifs stimulating sequence-specific TLR8-dependent immune responses. J Immunol 180 6 (2008) 3729-3738
36. Foster S.L., Hargreaves D.C., and Medzhitov R. Gene-specific control of inflammation by TLR-induced chromatin modifications. Nature 447 7147 (2007) 972-978
37. Frantz S., Kobzik L., Kim Y.D., Fukazawa R., Medzhitov R., Lee R.T., et al. Toll4 (TLR4) expression in cardiac myocytes in normal and failing myocardium. J Clin Invest 104 3 (1999) 271-280
38. Gallucci S., Lolkema M., and Matzinger P. Natural adjuvants: endogenous activators of dendritic cells. Nat Med 5 11 (1999) 1249-1255
39. Gao B., and Tsan M.F. Recombinant human heat shock protein 60 does not induce the release of tumor necrosis factor alpha from murine macrophages. J Biol Chem 278 25 (2003) 22523-22529
40. Gao B., and Tsan M.F. Endotoxin contamination in recombinant human heat shock protein 70 (Hsp70) preparation is responsible for the induction of tumor necrosis factor alpha release by murine macrophages. J Biol Chem 278 1 (2003) 174-179
41. Gay N.J., and Keith F.J. Drosophila Toll and IL-1 receptor. Nature 351 6325 (1991) 355-356
42. Gilliet M., Conrad C., Geiges M., Cozzio A., Thurlimann W., Burg G., et al. Psoriasis triggered by toll-like receptor 7 agonist imiquimod in the presence of dermal plasmacytoid dendritic cell precursors. Arch Dermatol 140 12 (2004) 1490-1495
43. Gorden K.B., Gorski K.S., Gibson S.J., Kedl R.M., Kieper W.C., Qiu X., et al. Synthetic TLR agonists reveal functional differences between human TLR7 and TLR8. J Immunol 174 3 (2005) 1259-1268
44. Gowen B.B., Hoopes J.D., Wong M.H., Jung K.H., Isakson K.C., Alexopoulou L., et al. TLR3 deletion limits mortality and disease severity due to Phlebovirus infection. J Immunol 177 9 (2006) 6301-6307
45. Hacker H., Redecke V., Blagoev B., Kratchmarova I., Hsu L.C., Wang G.G., et al. Specificity in Toll-like receptor signalling through distinct effector functions of TRAF3 and TRAF6. Nature 439 7073 (2006) 204-207
46. Hartmann G., Weiner G.J., and Krieg A.M. CpG DNA: a potent signal for growth, activation, and maturation of human dendritic cells. Proc Natl Acad Sci USA 96 16 (1999) 9305-9310
47. Hasan U., Chaffois C., Gaillard C., Saulnier V., Merck E., Tancredi S., et al. Human TLR10 is a functional receptor, expressed by B cells and plasmacytoid dendritic cells, which activates gene transcription through MyD88. J Immunol 174 5 (2005) 2942-2950
48. Hawn T.R., Wu H., Grossman J.M., Hahn B.H., Tsao B.P., and Aderem A. A stop codon polymorphism of Toll-like receptor 5 is associated with resistance to systemic lupus erythematosus. Proc Natl Acad Sci USA 102 30 (2005) 10593-10597
49. Hayashi F., Smith K.D., Ozinsky A., Hawn T.R., Yi E.C., Goodlett D.R., et al. The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature 410 6832 (2001) 1099-1103
50. Heil F., Hemmi H., Hochrein H., Ampenberger F., Kirschning C., Akira S., et al. Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8. Science 303 5663 (2004) 1526-1529
51. Hellman J., Tehan M.M., and Warren H.S. Murein lipoprotein, peptidoglycan-associated lipoprotein, and outer membrane protein A are present in purified rough and smooth lipopolysaccharides. J Infect Dis 188 2 (2003) 286-289
52. Hemmi H., Takeuchi O., Kawai T., Kaisho T., Sato S., Sanjo H., et al. A Toll-like receptor recognizes bacterial DNA. Nature 408 6813 (2000) 740-745
53. Hoebe K., Georgel P., Rutschmann S., Du X., Mudd S., Crozat K., et al. CD36 is a sensor of diacylglycerides. Nature 433 7025 (2005) 523-527
54. Honda K., Yanai H., Mizutani T., Negishi H., Shimada N., Suzuki N., et al. Role of a transductional-transcriptional processor complex involving MyD88 and IRF-7 in Toll-like receptor signaling. Proc Natl Acad Sci USA 101 43 (2004) 15416-15421
55. Horng T., Barton G.M., Flavell R.A., and Medzhitov R. The adaptor molecule TIRAP provides signalling specificity for Toll-like receptors. Nature 420 6913 (2002) 329-333
56. Hornung V., Rothenfusser S., Britsch S., Krug A., Jahrsdorfer B., Giese T., et al. Quantitative expression of toll-like receptor 1-10 mRNA in cellular subsets of human peripheral blood mononuclear cells and sensitivity to CpG oligodeoxynucleotides. J Immunol 168 9 (2002) 4531-4537
57. Hornung V., Guenthner-Biller M., Bourquin C., Ablasser A., Schlee M., Uematsu S., et al. Sequence-specific potent induction of IFN-alpha by short interfering RNA in plasmacytoid dendritic cells through TLR7. Nat Med 11 3 (2005) 263-270
58. Hornung V., Ellegast J., Kim S., Brzozka K., Jung A., Kato H., et al. 5′-Triphosphate RNA is the ligand for RIG-I. Science 314 5801 (2006) 994-997
59. Iwami K.I., Matsuguchi T., Masuda A., Kikuchi T., Musikacharoen T., and Yoshikai Y. Cutting edge: naturally occurring soluble form of mouse Toll-like receptor 4 inhibits lipopolysaccharide signaling. J Immunol 165 12 (2000) 6682-6686
60. Jack C.S., Arbour N., Manusow J., Montgrain V., Blain M., McCrea E., et al. TLR signaling tailors innate immune responses in human microglia and astrocytes. J Immunol 175 7 (2005) 4320-4330
61. Jack C., Ruffini F., Bar-Or A., and Antel J.P. Microglia and multiple sclerosis. J Neurosci Res 81 3 (2005) 363-373
62. Jackson A.C., Rossiter J.P., and Lafon M. Expression of Toll-like receptor 3 in the human cerebellar cortex in rabies, herpes simplex encephalitis, and other neurological diseases. J Neurovirol 12 3 (2006) 229-234
63. Janeway Jr. C.A. Approaching the asymptote? Evolution and revolution in immunology. Cold Spring Harb Symp Quant Biol 54 Pt 1 (1989) 1-13
64. Johnson G.B., Brunn G.J., Kodaira Y., and Platt J.L. Receptor-mediated monitoring of tissue well-being via detection of soluble heparan sulfate by Toll-like receptor 4. J Immunol 168 10 (2002) 5233-5239
65. Kadowaki N., Antonenko S., and Liu Y.J. Distinct CpG DNA and polyinosinic-polycytidylic acid double-stranded RNA, respectively, stimulate CD11c- type 2 dendritic cell precursors and CD11c+ dendritic cells to produce type I IFN. J Immunol 166 4 (2001) 2291-2295
66. Kagan J.C., Su T., Horng T., Chow A., Akira S., and Medzhitov R. TRAM couples endocytosis of Toll-like receptor 4 to the induction of interferon-beta. Nat Immunol 9 4 (2008) 361-368
67. Karimi K., Sarir H., Mortaz E., Smit J.J., Hosseini H., De Kimpe S.J., et al. Toll-like receptor-4 mediates cigarette smoke-induced cytokine production by human macrophages. Respir Res 7 (2006) 66
68. Katakura K., Lee J., Rachmilewitz D., Li G., Eckmann L., and Raz E. Toll-like receptor 9-induced type I IFN protects mice from experimental colitis. J Clin Invest 115 3 (2005) 695-702
69. Kielian T. Toll-like receptors in central nervous system glial inflammation and homeostasis. J Neurosci Res 83 5 (2006) 711-730
70. Komatsuda A., Wakui H., Iwamoto K., Ozawa M., Togashi M., Masai R., et al. Up-regulated expression of Toll-like receptors mRNAs in peripheral blood mononuclear cells from patients with systemic lupus erythematosus. Clin Exp Immunol (2008)
71. Konat G.W., Kielian T., and Marriott I. The role of Toll-like receptors in CNS response to microbial challenge. J Neurochem 99 1 (2006) 1-12
72. Kurt-Jones E.A., Chan M., Zhou S., Wang J., Reed G., Bronson R., et al. Herpes simplex virus 1 interaction with Toll-like receptor 2 contributes to lethal encephalitis. Proc Natl Acad Sci USA 101 5 (2004) 1315-1320
73. Kyburz D., Brentano F., and Gay S. Mode of action of hydroxychloroquine in RA-evidence of an inhibitory effect on toll-like receptor signaling. Nat Clin Pract Rheumatol 2 9 (2006) 458-459
74. Lafon M., Megret F., Lafage M., and Prehaud C. The innate immune facet of brain: human neurons express TLR-3 and sense viral dsRNA. J Mol Neurosci 29 3 (2006) 185-194
75. Lang K.S., Georgiev P., Recher M., Navarini A.A., Bergthaler A., Heikenwalder M., et al. Immunoprivileged status of the liver is controlled by Toll-like receptor 3 signaling. J Clin Invest 116 9 (2006) 2456-2463
76. Lau C.M., Broughton C., Tabor A.S., Akira S., Flavell R.A., Mamula M.J., et al. RNA-associated autoantigens activate B cells by combined B cell antigen receptor/Toll-like receptor 7 engagement. J Exp Med 202 9 (2005) 1171-1177
77. Le Goffic R., Balloy V., Lagranderie M., Alexopoulou L., Escriou N., Flavell R., et al. Detrimental contribution of the Toll-like receptor (TLR)3 to influenza A virus-induced acute pneumonia. PLoS Pathog 2 6 (2006) e53
78. Leadbetter E.A., Rifkin I.R., Hohlbaum A.M., Beaudette B.C., Shlomchik M.J., and Marshak-Rothstein A. Chromatin-IgG complexes activate B cells by dual engagement of IgM and Toll-like receptors. Nature 416 6881 (2002) 603-607
79. LeBouder E., Rey-Nores J.E., Rushmere N.K., Grigorov M., Lawn S.D., Affolter M., et al. Soluble forms of Toll-like receptor (TLR)2 capable of modulating TLR2 signaling are present in human plasma and breast milk. J Immunol 171 12 (2003) 6680-6689
80. Lebre M.C., van der Aar A.M., van Baarsen L., van Capel T.M., Schuitemaker J.H., Kapsenberg M.L., et al. Human keratinocytes express functional Toll-like receptor 3, 4, 5, and 9. J Invest Dermatol 127 2 (2007) 331-341
81. Lee H.K., Lee J., and Tobias P.S. Two lipoproteins extracted from Escherichia coli K-12 LCD25 lipopolysaccharide are the major components responsible for Toll-like receptor 2-mediated signaling. J Immunol 168 8 (2002) 4012-4017
82. Lee H.K., Dunzendorfer S., Soldau K., and Tobias P.S. Double-stranded RNA-mediated TLR3 activation is enhanced by CD14. Immunity 24 2 (2006) 153-163
83. Lee J., Mo J.H., Katakura K., Alkalay I., Rucker A.N., Liu Y.T., et al. Maintenance of colonic homeostasis by distinctive apical TLR9 signalling in intestinal epithelial cells. Nat Cell Biol 8 12 (2006) 1327-1336
84. Lee J., Rachmilewitz D., and Raz E. Homeostatic effects of TLR9 signaling in experimental colitis. Ann N Y Acad Sci 1072 (2006) 351-355
85. Lemaitre B., Nicolas E., Michaut L., Reichhart J.M., and Hoffmann J.A. The dorsoventral regulatory gene cassette spatzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell 86 6 (1996) 973-983
86. Liu Z.Q., Deng G.M., Foster S., and Tarkowski A. Staphylococcal peptidoglycans induce arthritis. Arthritis Res 3 6 (2001) 375-380
87. Liu L., Botos I., Wang Y., Leonard J.N., Shiloach J., Segal D.M., et al. Structural basis of toll-like receptor 3 signaling with double-stranded RNA. Science 320 5874 (2008) 379-381
88. Massari P., Visintin A., Gunawardana J., Halmen K.A., King C.A., Golenbock D.T., et al. Meningococcal porin PorB binds to TLR2 and requires TLR1 for signaling. J Immunol 176 4 (2006) 2373-2380
89. Matsumoto M., Kikkawa S., Kohase M., Miyake K., and 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 5 (2002) 1364-1369
90. Matzinger P. Tolerance, danger, and the extended family. Annu Rev Immunol 12 (1994) 991-1045
91. Means T.K., Latz E., Hayashi F., Murali M.R., Golenbock D.T., and Luster A.D. Human lupus autoantibody-DNA complexes activate DCs through cooperation of CD32 and TLR9. J Clin Invest 115 2 (2005) 407-417
92. Medzhitov R., Preston-Hurlburt P., and Janeway Jr. C.A. A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 388 6640 (1997) 394-397
93. Mizel S.B., Honko A.N., Moors M.A., Smith P.S., and West A.P. Induction of macrophage nitric oxide production by Gram-negative flagellin involves signaling via heteromeric Toll-like receptor 5/Toll-like receptor 4 complexes. J Immunol 170 12 (2003) 6217-6223
94. Negishi H., Fujita Y., Yanai H., Sakaguchi S., Ouyang X., Shinohara M., et al. Evidence for licensing of IFN-gamma-induced IFN regulatory factor 1 transcription factor by MyD88 in Toll-like receptor-dependent gene induction program. Proc Natl Acad Sci USA 103 41 (2006) 15136-15141
95. Newman R.M., Salunkhe P., Godzik A., and Reed J.C. Identification and characterization of a novel bacterial virulence factor that shares homology with mammalian Toll/interleukin-1 receptor family proteins. Infect Immun 74 1 (2006) 594-601
96. Nikolaus S., Rutgeerts P., Fedorak R., Steinhart A.H., Wild G.E., Theuer D., et al. Interferon beta-1a in ulcerative colitis: a placebo controlled, randomised, dose escalating study. Gut 52 9 (2003) 1286-1290
97. Nusinzon I., and Horvath C.M. Positive and negative regulation of the innate antiviral response and beta interferon gene expression by deacetylation. Mol Cell Biol 26 8 (2006) 3106-3113
98. Ogura Y., Bonen D.K., Inohara N., Nicolae D.L., Chen F.F., Ramos R., et al. A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature 411 6837 (2001) 603-606
99. Okamura Y., Watari M., Jerud E.S., Young D.W., Ishizaka S.T., Rose J., et al. The extra domain A of fibronectin activates Toll-like receptor 4. J Biol Chem 276 13 (2001) 10229-10233
100. Ouaissi A., Guilvard E., Delneste Y., Caron G., Magistrelli G., Herbault N., et al. The Trypanosoma cruzi Tc52-released protein induces human dendritic cell maturation, signals via Toll-like receptor 2, and confers protection against lethal infection. J Immunol 168 12 (2002) 6366-6374
101. Ozinsky A., Underhill D.M., Fontenot J.D., Hajjar A.M., Smith K.D., Wilson C.B., 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 97 25 (2000) 13766-13771
102. Papadimitraki E.D., Choulaki C., Koutala E., Bertsias G., Tsatsanis C., Gergianaki I., et al. Expansion of toll-like receptor 9-expressing B cells in active systemic lupus erythematosus: implications for the induction and maintenance of the autoimmune process. Arthritis Rheum 54 11 (2006) 3601-3611
103. Park Y., Park S., Yoo E., Kim D., and Shin H. Association of the polymorphism for Toll-like receptor 2 with type 1 diabetes susceptibility. Ann N Y Acad Sci 1037 (2004) 170-174
104. Park J.S., Gamboni-Robertson F., He Q., Svetkauskaite D., Kim J.Y., Strassheim D., et al. High mobility group box 1 protein interacts with multiple Toll-like receptors. Am J Physiol Cell Physiol 290 3 (2006) C917-C924
105. Patole P.S., Grone H.J., Segerer S., Ciubar R., Belemezova E., Henger A., et al. Viral double-stranded RNA aggravates lupus nephritis through Toll-like receptor 3 on glomerular mesangial cells and antigen-presenting cells. J Am Soc Nephrol 16 5 (2005) 1326-1338
106. Pierer M., Rethage J., Seibl R., Lauener R., Brentano F., Wagner U., et al. Chemokine secretion of rheumatoid arthritis synovial fibroblasts stimulated by Toll-like receptor 2 ligands. J Immunol 172 2 (2004) 1256-1265
107. Pirie F.J., Pegoraro R., Motala A.A., Rauff S., Rom L., Govender T., et al. Toll-like receptor 3 gene polymorphisms in South African Blacks with type 1 diabetes. Tissue Antigens 66 2 (2005) 125-130
108. Pope R.M., and Tschopp J. The role of interleukin-1 and the inflammasome in gout: implications for therapy. Arthritis Rheum 56 10 (2007) 3183-3188
109. Prens E.P., Kant M., van Dijk G., van der Wel L.I., Mourits S., and van der Fits L. IFN-alpha enhances poly-IC responses in human keratinocytes by inducing expression of cytosolic innate RNA receptors: relevance for psoriasis. J Invest Dermatol 128 4 (2008) 932-938
110. Prinz M., Garbe F., Schmidt H., Mildner A., Gutcher I., Wolter K., et al. Innate immunity mediated by TLR9 modulates pathogenicity in an animal model of multiple sclerosis. J Clin Invest 116 2 (2006) 456-464
111. Pryshchep O., Ma-Krupa W., Younge B.R., Goronzy J.J., and Weyand C.M. Vessel-specific Toll-like receptor profiles in human medium and large arteries. Circulation 118 12 (2008) 1276-1284
112. Radstake T.R., Roelofs M.F., Jenniskens Y.M., Oppers-Walgreen B., van Riel P.L., Barrera P., et al. Expression of toll-like receptors 2 and 4 in rheumatoid synovial tissue and regulation by proinflammatory cytokines interleukin-12 and interleukin-18 via interferon-gamma. Arthritis Rheum 50 12 (2004) 3856-3865
113. Rajan N., and Langtry J.A. Generalized exacerbation of psoriasis associated with imiquimod cream treatment of superficial basal cell carcinomas. Clin Exp Dermatol 31 1 (2006) 140-141
114. Rakoff-Nahoum S., Paglino J., Eslami-Varzaneh F., Edberg S., and Medzhitov R. Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell 118 2 (2004) 229-241
115. Rock F.L., Hardiman G., Timans J.C., Kastelein R.A., and Bazan J.F. A family of human receptors structurally related to Drosophila Toll. Proc Natl Acad Sci USA 95 2 (1998) 588-593
116. Roelofs M.F., Joosten L.A., Abdollahi-Roodsaz S., van Lieshout A.W., Sprong T., van den Hoogen F.H., et al. The expression of toll-like receptors 3 and 7 in rheumatoid arthritis synovium is increased and costimulation of toll-like receptors 3, 4, and 7/8 results in synergistic cytokine production by dendritic cells. Arthritis Rheum 52 8 (2005) 2313-2322
117. Roelofs M.F., Boelens W.C., Joosten L.A., Abdollahi-Roodsaz S., Geurts J., Wunderink L.U., et al. Identification of small heat shock protein B8 (HSP22) as a novel TLR4 ligand and potential involvement in the pathogenesis of rheumatoid arthritis. J Immunol 176 11 (2006) 7021-7027
118. Sadeghi K., Wessner B., Laggner U., Ploder M., Tamandl D., Friedl J., et al. Vitamin D3 down-regulates monocyte TLR expression and triggers hyporesponsiveness to pathogen-associated molecular patterns. Eur J Immunol 36 2 (2006) 361-370
119. Salmaggi A., Gelati M., Dufour A., Corsini E., Pagano S., Baccalini R., et al. Expression and modulation of IFN-gamma-inducible chemokines (IP-10, Mig, and I-TAC) in human brain endothelium and astrocytes: possible relevance for the immune invasion of the central nervous system and the pathogenesis of multiple sclerosis. J Interferon Cytokine Res 22 6 (2002) 631-640
120. Sato Y., Miyata M., Sato Y., Nishimaki T., Kochi H., and Kasukawa R. CpG motif-containing DNA fragments from sera of patients with systemic lupus erythematosus proliferate mononuclear cells in vitro. J Rheumatol 26 2 (1999) 294-301
121. Schauber J., Dorschner R.A., Coda A.B., Buchau A.S., Liu P.T., Kiken D., et al. Injury enhances TLR2 function and antimicrobial peptide expression through a vitamin D-dependent mechanism. J Clin Invest 117 3 (2007) 803-811
122. Schwandner R., Dziarski R., Wesche H., Rothe M., and Kirschning C.J. Peptidoglycan- and lipoteichoic acid-induced cell activation is mediated by toll-like receptor 2. J Biol Chem 274 25 (1999) 17406-17409
123. Seibl R., Birchler T., Loeliger S., Hossle J.P., Gay R.E., Saurenmann T., et al. Expression and regulation of Toll-like receptor 2 in rheumatoid arthritis synovium. Am J Pathol 162 4 (2003) 1221-1227
124. Shi Y., Zheng W., and Rock K.L. Cell injury releases endogenous adjuvants that stimulate cytotoxic T cell responses. Proc Natl Acad Sci USA 97 26 (2000) 14590-14595
125. Shigeoka A.A., Holscher T.D., King A.J., Hall F.W., Kiosses W.B., Tobias P.S., et al. TLR2 is constitutively expressed within the kidney and participates in ischemic renal injury through both MyD88-dependent and -independent pathways. J Immunol 178 10 (2007) 6252-6258
126. 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 189 11 (1999) 1777-1782
127. Smiley S.T., King J.A., and Hancock W.W. Fibrinogen stimulates macrophage chemokine secretion through toll-like receptor 4. J Immunol 167 5 (2001) 2887-2894
128. Song P.I., Park Y.M., Abraham T., Harten B., Zivony A., Neparidze N., et al. Human keratinocytes express functional CD14 and toll-like receptor 4. J Invest Dermatol 119 2 (2002) 424-432
129. Szebeni B., Veres G., Dezsofi A., Rusai K., Vannay A., Mraz M., et al. Increased expression of Toll-like receptor (TLR) 2 and TLR4 in the colonic mucosa of children with inflammatory bowel disease. Clin Exp Immunol 151 1 (2008) 34-41
130. Takaoka A., Yanai H., Kondo S., Duncan G., Negishi H., Mizutani T., et al. Integral role of IRF-5 in the gene induction programme activated by Toll-like receptors. Nature 434 7030 (2005) 243-249
131. 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 169 1 (2002) 10-14
132. Takeuchi J., Watari E., Shinya E., Norose Y., Matsumoto M., Seya T., et al. Down-regulation of Toll-like receptor expression in monocyte-derived Langerhans cell-like cells: implications of low-responsiveness to bacterial components in the epidermal Langerhans cells. Biochem Biophys Res Commun 306 3 (2003) 674-679
133. 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 195 1 (2002) 99-111
134. Tissari J., Siren J., Meri S., Julkunen I., and Matikainen S. IFN-alpha enhances TLR3-mediated antiviral cytokine expression in human endothelial and epithelial cells by up-regulating TLR3 expression. J Immunol 174 7 (2005) 4289-4294
135. Torok H.P., Glas J., Tonenchi L., Bruennler G., Folwaczny M., and Folwaczny C. Crohn's disease is associated with a toll-like receptor-9 polymorphism. Gastroenterology 127 1 (2004) 365-366
136. Touil T., Fitzgerald D., Zhang G.X., Rostami A., and Gran B. Cutting Edge: TLR3 stimulation suppresses experimental autoimmune encephalomyelitis by inducing endogenous IFN-beta. J Immunol 177 11 (2006) 7505-7509
137. Tse K., and Horner A.A. Update on toll-like receptor-directed therapies for human disease. Ann Rheum Dis 66 Suppl. 3 (2007) iii77-iii80
138. Uehara A., Fujimoto Y., Fukase K., and Takada H. Various human epithelial cells express functional Toll-like receptors, NOD1 and NOD2 to produce anti-microbial peptides, but not proinflammatory cytokines. Mol Immunol 44 12 (2007) 3100-3111
139. Underhill D.M., Ozinsky A., Smith K.D., and Aderem A. Toll-like receptor-2 mediates mycobacteria-induced proinflammatory signaling in macrophages. Proc Natl Acad Sci USA 96 25 (1999) 14459-14463
140. Vabulas R.M., Ahmad-Nejad P., da Costa C., Miethke T., Kirschning C.J., Hacker H., et al. 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 33 (2001) 31332-31339
141. Vabulas R.M., Ahmad-Nejad P., Ghose S., Kirschning C.J., Issels R.D., and Wagner H. HSP70 as endogenous stimulus of the Toll/interleukin-1 receptor signal pathway. J Biol Chem 277 17 (2002) 15107-15112
142. van der Kleij D., Latz E., Brouwers J.F., Kruize Y.C., Schmitz M., Kurt-Jones E.A., et al. A novel host-parasite lipid cross-talk. Schistosomal lyso-phosphatidylserine activates toll-like receptor 2 and affects immune polarization. J Biol Chem 277 50 (2002) 48122-48129
143. Vanags D., Williams B., Johnson B., Hall S., Nash P., Taylor A., et al. Therapeutic efficacy and safety of chaperonin 10 in patients with rheumatoid arthritis: a double-blind randomised trial. Lancet 368 9538 (2006) 855-863
144. Vasselon T., Detmers P.A., Charron D., and Haziot A. TLR2 recognizes a bacterial lipopeptide through direct binding. J Immunol 173 12 (2004) 7401-7405
145. Viglianti G.A., Lau C.M., Hanley T.M., Miko B.A., Shlomchik M.J., and Marshak-Rothstein A. Activation of autoreactive B cells by CpG dsDNA. Immunity 19 6 (2003) 837-847
146. Vijay-Kumar M., Wu H., Aitken J., Kolachala V.L., Neish A.S., Sitaraman S.V., et al. Activation of toll-like receptor 3 protects against DSS-induced acute colitis. Inflamm Bowel Dis 13 7 (2007) 856-864
147. Wallin R.P., Lundqvist A., More S.H., von Bonin A., Kiessling R., and Ljunggren H.G. Heat-shock proteins as activators of the innate immune system. Trends Immunol 23 3 (2002) 130-135
148. Wang T., Town T., Alexopoulou L., Anderson J.F., Fikrig E., and Flavell R.A. Toll-like receptor 3 mediates West Nile virus entry into the brain causing lethal encephalitis. Nat Med 10 12 (2004) 1366-1373
149. Wang J.P., Kurt-Jones E.A., Shin O.S., Manchak M.D., Levin M.J., and Finberg R.W. Varicella-zoster virus activates inflammatory cytokines in human monocytes and macrophages via Toll-like receptor 2. J Virol 79 20 (2005) 12658-12666
150. Watters T.M., Kenny E.F., and O'Neill L.A. Structure, function and regulation of the Toll/IL-1 receptor adaptor proteins. Immunol Cell Biol 85 6 (2007) 411-419
151. Watts C. Location, location, location: identifying the neighborhoods of LPS signaling. Nat Immunol 9 4 (2008) 343-345
152. Wehkamp J., Harder J., Weichenthal M., Schwab M., Schaffeler E., Schlee M., et al. NOD2 (CARD15) mutations in Crohn's disease are associated with diminished mucosal alpha-defensin expression. Gut 53 11 (2004) 1658-1664
153. Wen L., Peng J., Li Z., and Wong F.S. The effect of innate immunity on autoimmune diabetes and the expression of Toll-like receptors on pancreatic islets. J Immunol 172 5 (2004) 3173-3180
154. Wetzler L.M. The role of Toll-like receptor 2 in microbial disease and immunity. Vaccine 21 Suppl. 2 (2003) S55-S60
155. Wu J.K., Siller G., and Strutton G. Psoriasis induced by topical imiquimod. Australas J Dermatol 45 1 (2004) 47-50
156. Wyllie D.H., Kiss-Toth E., Visintin A., Smith S.C., Boussouf S., Segal D.M., et al. Evidence for an accessory protein function for Toll-like receptor 1 in anti-bacterial responses. J Immunol 165 12 (2000) 7125-7132
157. Yamamoto M., Sato S., Mori K., Hoshino K., Takeuchi O., Takeda K., et al. Cutting edge: a novel Toll/IL-1 receptor domain-containing adapter that preferentially activates the IFN-beta promoter in the Toll-like receptor signaling. J Immunol 169 12 (2002) 6668-6672
158. Yamamoto M., Sato S., Hemmi H., Hoshino K., Kaisho T., Sanjo H., et al. Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway. Science 301 5633 (2003) 640-643
159. Yang D., Chen Q., Su S.B., Zhang P., Kurosaka K., Caspi R.R., et al. Eosinophil-derived neurotoxin acts as an alarmin to activate the TLR2-MyD88 signal pathway in dendritic cells and enhances Th2 immune responses. J Exp Med 205 1 (2008) 79-90
160. Zahringer U., Lindner B., Inamura S., Heine H., and Alexander C. TLR2-promiscuous or specific? A critical re-evaluation of a receptor expressing apparent broad specificity. Immunobiology 213 3-4 (2008) 205-224
161. Zare F., Bokarewa M., Nenonen N., Bergstrom T., Alexopoulou L., Flavell R.A., et al. Arthritogenic properties of double-stranded (viral) RNA. J Immunol 172 9 (2004) 5656-5663
162. Zeng H., Wu H., Sloane V., Jones R., Yu Y., Lin P., et al. Flagellin/TLR5 responses in epithelia reveal intertwined activation of inflammatory and apoptotic pathways. Am J Physiol Gastrointest Liver Physiol 290 1 (2006) G96-G108