Advances in Toll-like receptor biology: Modes of activation by diverse stimuli

Critical Reviews in Biochemistry and Molecular Biology

Volumn 50, Issue 5, 2015, Pages 359-379

  Bryant, Clare E ^a   Gay, Nick J ^a   Heymans, Stephane ^b,c   Sacre, Sandra ^d   Schaefer, Liliana ^e   Midwood, Kim S ^f  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^b UNIVERSITY OF LEUVEN   (Belgium)

^c ROYAL NETHERLANDS ACADEMY OF ARTS AND SCIENCES   (Netherlands)

^d UNIVERSITY OF SUSSEX   (United Kingdom)

^e UNIVERSITY HOSPITAL FRANKFURT   (Germany)

^f UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

Allergens; endogenous stimuli; extracellular matrix glycoproteins; nucleic acids; pathogen recognition; small leucine rich proteoglycans; structure; Toll like receptors

Indexed keywords

BIGLYCAN; DECORIN; GLYCOPROTEIN; LUMICAN; OSTEOGLYCIN; PROTEOGLYCAN; SMALL LEUCINE RICH PROTEOGLYCAN; TOLL LIKE RECEPTOR; TOLL LIKE RECEPTOR AGONIST; UNCLASSIFIED DRUG; ALLERGEN; ISOPROTEIN; LIGAND;

CLINICAL TRIAL (TOPIC); ENDOSOME; EXTRACELLULAR MATRIX; FEEDBACK SYSTEM; HEART DISEASE; HUMAN; IMMUNITY; IMMUNOLOGICAL MEMORY; INFLAMMATION; MOLECULAR INTERACTION; MOLECULAR RECOGNITION; NEPHRITIS; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN STRUCTURE; REVIEW; SIGNAL TRANSDUCTION; STIMULUS; AGONISTS; ANIMAL; AUTOIMMUNITY; BIOLOGICAL MODEL; CHEMISTRY; IMMUNOLOGY; INNATE IMMUNITY; MACROPHAGE; METABOLISM; PROTEIN CONFORMATION;

ALLERGENS; ANIMALS; AUTOIMMUNITY; EXTRACELLULAR MATRIX; HUMANS; IMMUNITY, INNATE; LIGANDS; MACROPHAGES; MODELS, BIOLOGICAL; PROTEIN CONFORMATION; PROTEIN ISOFORMS; SIGNAL TRANSDUCTION; TOLL-LIKE RECEPTORS;

EID: 84944066432     PISSN: 10409238     EISSN: 15497798     Source Type: Journal    
DOI: 10.3109/10409238.2015.1033511     Document Type: Review

References (236)

1. Abdi J, Engels F, Garssen, J, Redegeld FA. (2011). Toll-like receptor-9 triggering modulates expression of alpha-4 integrin on human B lymphocytes and their adhesion to extracellular matrix proteins. Exp Hematol 39: 927-33
2. Ahmad-Nejad P, Mrabet-Dahbi S, Breuer K, et al. (2004). The Toll-like receptor 2 R753Q polymorphism defines a subgroup of patients with atopic dermatitis having severe phenotype. J Allergy Clin Immunol 113: 565-7
3. Alexopoulou L, Holt AC, Medzhitov R, Flavell RA. (2001). Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature 413: 732-8
4. Alvarado J, Taylor P, Castillo JR, Thomas LE. (2005). Interferon gamma bound to extracellular matrix changes the hyporesponsiveness to LPS in crypt but not villous intestinal epithelial cells. Immunol Lett 99: 109-12
5. Anders HJ, Schaefer L. (2014). Beyond tissue injury-damage-associated molecular patterns, toll-like receptors, and inflammasomes also drive regeneration and fibrosis. J Am Soc Nephrol 25: 1387-400
6. Antia M, Baneyx G, Kubow KE, Vogel V. (2008). Fibronectin in aging extracellular matrix fibrils is progressively unfolded by cells and elicits an enhanced rigidity response. Faraday Discuss 139: 229-49; discussion 309-25, 419-20
7. Arbour NC, Lorenz E, Schutte BC, et al. (2000). TLR4 mutations are associated with endotoxin hyporesponsiveness in humans. Nat Genet 25: 187-91
8. Arribillaga L, Durantez M, Lozano T, et al. (2013). A fusion protein between streptavidin and the endogenous TLR4 ligand EDA targets biotinylated antigens to dendritic cells and induces T cell responses in vivo. Biomed Res Int 2013: 864720
9. Aryan Z, Holgate ST, Radzioch D, Rezaei N. (2014). A new era of targeting the ancient gatekeepers of the immune system: Toll-like agonists in the treatment of allergic rhinitis and asthma. Int Arch Allergy Immunol 164: 46-63
10. Ayada Y, Kusachi S, Murakami T, et al. (2001). Increased expression of biglycan mRNA in pressure-overloaded rat heart. Clin Exp Hypertens 23: 633-43
11. Baba H, Ishiwata T, Takashi E, et al. (2001). Expression and localization of lumican in the ischemic and reperfused rat heart. Jpn Circ J 65: 445-50
12. Babelova A, Moreth K, Tsalastra-Greul W, et al. (2009). Biglycan, a danger signal that activates the NLRP3 inflammasome via Toll-like and P2X receptors. J Biol Chem 284: 24035-48
13. Barrera V, Skorokhod OA, Baci D, et al. (2011). Host fibrinogen stably bound to hemozoin rapidly activates monocytes via TLR-4 and CD11b/CD18-integrin: a new paradigm of hemozoin action. Blood 117: 5674-82
14. Baumann CL, Aspalter IM, Sharif O, et al. (2010). CD14 is a coreceptor of Toll-like receptors 7 and 9. J Exp Med 207: 2689-701
15. Bereczki E, Gonda S, Csont T, et al. (2007). Overexpression of biglycan in the heart of transgenic mice: an antibody microarray study. J Proteome Res 6: 854-61
16. Bhattacharyya S, Tamaki Z, Wang W, et al. (2014). FibronectinEDA promotes chronic cutaneous fibrosis through Toll-like receptor signaling. Sci Transl Med 6: 232ra50
17. Bryant CE, Spring DR, Gangloff M, Gay NJ. (2010). The molecular basis of the host response to lipopolysaccharide. Nat Rev Microbiol 8: 8-14
18. Carlson EC, Lin M, Liu CY, et al. (2007). Keratocan and lumican regulate neutrophil infiltration and corneal clarity in lipopolysaccharide-induced keratitis by direct interaction with CXCL1. J Biol Chem 282: 35502-9
19. Carpenter S, Wochal P, Dunne A, O'Neill LA. (2011). Toll-like receptor 3 (TLR3) signaling requires TLR4 interactor with leucine-rich REPeats (TRIL). J Biol Chem 286: 38795-804
20. Casi G, Neri D. (2012). Antibody-drug conjugates: basic concepts, examples and future perspectives. J Control Release 161: 422-8
21. Casrouge A, Zhang SY, Eidenschenk C, et al. (2006). Herpes simplex virus encephalitis in human UNC-93B deficiency. Science 314: 308-12
22. Chan JK, Roth J, Oppenheim JJ, et al. (2012). Alarmins: awaiting a clinical response. J Clin Invest 122: 2711-19
23. Chapman MD, Pomes A, Breiteneder H, Ferreira F. (2007). Nomenclature and structural biology of allergens. J Allergy Clin Immunol 119: 414-20
24. Chen S, Birk DE. (2013). The regulatory roles of small leucine-rich proteoglycans in extracellular matrix assembly. FEBS J 280: 2120-37
25. Cheng G, Swaidani S, Sharma M, et al. (2013). Correlation of hyaluronan deposition with infiltration of eosinophils and lymphocytes in a cockroach-induced murine model of asthma. Glycobiology 23: 43-58
26. Chiquet-Ehrismann R, Orend G, Chiquet M, et al. (2014). Tenascins in stem cell niches. Matrix Biol 37: 112-23
27. Chockalingam A, Brooks JC, Cameron JL, et al. (2009). TLR9 traffics through the Golgi complex to localize to endolysosomes and respond to CpG DNA. Immunol Cell Biol 87: 209-17
28. Chung KJ, Mitroulis I, Wiessner JR, et al. (2014). A novel pathway of rapid TLR-triggered activation of integrin-dependent leukocyte adhesion that requires Rap1 GTPase. Mol Biol Cell 25: 2948-55
29. Csont T, Gorbe A, Bereczki E, et al. (2010). Biglycan protects cardiomyocytes against hypoxia/reoxygenation injury: role of nitric oxide. J Mol Cell Cardiol 48: 649-52
30. De Bouteiller O, Merck E, Hasan UA, et al. (2005). Recognition of double-stranded RNA by human Toll-like receptor 3 and downstream receptor signaling requires multimerization and an acidic pH. J Biol Chem 280: 38133-45
31. De Haan JJ, Smeets MB, Pasterkamp G, Arslan F. (2013). Danger signals in the initiation of the inflammatory response after myocardial infarction. Mediators Inflamm 2013: 206039
32. Demaria O, Pagni PP, Traub S, et al. (2010). TLR8 deficiency leads to autoimmunity in mice. J Clin Invest 120: 3651-62
33. Diebold SS, Kaisho T, Hemmi H, et al. (2004). Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. Science 303: 1529-31
34. Doll F, Schwager K, Hemmerle T, Neri D. (2013). Murine analogues of etanercept and of F8-IL10 inhibit the progression of collagen-induced arthritis in the mouse. Arthritis Res Ther 15: R138
35. Doz E, Rose S, Nigou J, et al. (2007). Acylation determines the Toll-like receptor (TLR)-dependent positive versus TLR2-, mannose receptor-, and SIGNR1-independent negative regulation of pro-inflammatory cytokines by mycobacterial lipomannan. J Biol Chem 282: 26014-25
36. Eberle F, Sirin M, Binder M, Dalpke AH. (2009). Bacterial RNA is recognized by different sets of immunoreceptors. Eur J Immunol 39: 2537-47
37. Eder W, Klimecki W, Yu L, et al. (2004). Toll-like receptor 2 as a major gene for asthma in children of European farmers. J Allergy Clin Immunol 113: 482-8
38. Edwards L, Ferenczy A, Eron L, et al. (1998). Self-administered topical 5% imiquimod cream for external anogenital warts. HPV Study Group. Human PapillomaVirus. Arch Dermatol 134: 25-30
39. El-Omar EM, Ng MT, Hold GL. (2008). Polymorphisms in Toll-like receptor genes and risk of cancer. Oncogene 27: 244-52
40. Ewald SE, Engel A, Lee J, et al. (2011). Nucleic acid recognition by Toll-like receptors is coupled to stepwise processing by cathepsins and asparagine endopeptidase. J Exp Med 208: 643-51
41. Ewald SE, Lee BL, Lau L, et al. (2008). The ectodomain of Toll-like receptor 9 is cleaved to generate a functional receptor. Nature 456: 658-62
42. Fabbri M, Paone A, Calore F, et al. (2012). MicroRNAs bind to Toll-like receptors to induce prometastatic inflammatory response. Proc Natl Acad Sci USA 109: E2110-16
43. Frantz S, Kobzik L, Kim YD, et al. (1999). Toll4 (TLR4) expression in cardiac myocytes in normal and failing myocardium. J Clin Invest 104: 271-80
44. Frey H, Schroeder N, Manon-Jensen T, et al. (2013). Biological interplay between proteoglycans and their innate immune receptors in inflammation. FEBS J 280: 2165-79
45. Fujimoto M, Suzuki H, Shiba M, et al. (2013). Tenascin-C induces prolonged constriction of cerebral arteries in rats. Neurobiol Dis 55: 104-9
46. Fukui R, Saitoh S, Matsumoto F, et al. (2009). Unc93B1 biases Toll-like receptor responses to nucleic acid in dendritic cells toward DNA- but against RNA-sensing. J Exp Med 206: 1339-50
47. Gangloff M, Gay NJ. (2004). MD-2: the Toll gatekeeper' in endotoxin signalling. Trends Biochem Sci 29: 294-300
48. Ganguly D, Chamilos G, Lande R, et al. (2009). Self-RNA-antimicrobial peptide complexes activate human dendritic cells through TLR7 and TLR8. J Exp Med 206: 1983-94
49. Gay NJ, Gangloff M, O'Neill LA. (2011). What the Myddosome structure tells us about the initiation of innate immunity. Trends Immunol 32: 104-9
50. Gay NJ, Gangloff M. (2007). Structure and function of Toll receptors and their ligands. Annu Rev Biochem 76: 141-65
51. Geisse J, Caro I, Lindholm J, et al. (2004). Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: results from two phase III, randomized, vehicle-controlled studies. J Am Acad Dermatol 50: 722-33
52. Gibbard RJ, Morley PJ, Gay NJ. (2006). Conserved features in the extracellular domain of human Toll-like receptor 8 are essential for pH-dependent signaling. J Biol Chem 281: 27503-11
53. Goh FG, Piccinini AM, Krausgruber T, et al. (2010). Transcriptional regulation of the endogenous danger signal tenascin-C: a novel autocrine loop in inflammation. J Immunol 184: 2655-62
54. Gondokaryono SP, Ushio H, Niyonsaba F, et al. (2007). The extra domain A of fibronectin stimulates murine mast cells via Toll-like receptor 4. J Leukoc Biol 82: 657-65
55. Gorden KK, Qiu XX, Binsfeld CC, et al. (2006). Cutting edge: activation of murine TLR8 by a combination of imidazoquinoline immune response modifiers and polyT oligodeoxynucleotides. J Immunol 177: 6584-7
56. Govindaraj RG, Manavalan B, Basith S, Choi S. (2011). Comparative analysis of species-specific ligand recognition in Toll-like receptor 8 signaling: a hypothesis. PLoS One 6: e25118
57. Green DS, Bodman-Smith MD, Dalgleish AG, Fischer MD. (2007). Phase I/II study of topical imiquimod and intralesional interleukin-2 in the treatment of accessible metastases in malignant melanoma. Br J Dermatol 156: 337-45
58. Guo Y, Audry M, Ciancanelli M, et al. (2011). Herpes simplex virus encephalitis in a patient with complete TLR3 deficiency: TLR3 is otherwise redundant in protective immunity. J Exp Med 208: 2083-98
59. Haas T, Metzger J, Schmitz F, et al. (2008). The DNA sugar backbone 2′ deoxyribose determines Toll-like receptor 9 activation. Immunity 28: 315-23
60. Hacker G, Redecke V, Hacker H. (2002). Activation of the immune system by bacterial CpG-DNA. Immunology 105: 245-51
61. Haglund L, Bernier SM, Onnerfjord P, Recklies AD. (2008). Proteomic analysis of the LPS-induced stress response in rat chondrocytes reveals induction of innate immune response components in articular cartilage. Matrix Biol 27: 107-18
62. Hammad H, Chieppa M, Perros F, et al. (2009). House dust mite allergen induces asthma via Toll-like receptor 4 triggering of airway structural cells. Nat Med 15: 410-16
63. Hao J, Ju H, Zhao S, et al. (1999). Elevation of expression of Smads 2, 3, and 4, decorin and TGF-beta in the chronic phase of myocardial infarct scar healing. J Mol Cell Cardiol 31: 667-78
64. Heil F, Hemmi H, Hochrein H, et al. (2004). Species-specific recognition of single-stranded RNA via Toll-like receptor 7 and 8. Science 303: 1526-9
65. Hemmerle T, Doll F, Neri D. (2014). Antibody-based delivery of IL4 to the neovasculature cures mice with arthritis. Proc Natl Acad Sci USA 111: 12008-12
66. Hemmi H, Kaisho T, Takeuchi O, et al. (2002). Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway. Nat Immunol 3: 196-200
67. Henderson B, Nair S, Pallas J, Williams MA. (2011). Fibronectin: a multidomain host adhesin targeted by bacterial fibronectin-binding proteins. FEMS Microbiol Rev 35: 147-200
68. Hennessy EJ, Parker AE, O'Neill LA. (2010). Targeting Toll-like receptors: emerging therapeutics? Nat Rev Drug Discov 9: 293-307
69. Hepburn L, Prajsnar TK, Klapholz C, et al. (2014). Innate immunity. A Spaetzle-like role for nerve growth factor beta in vertebrate immunity to Staphylococcus aureus. Science 346: 641-6
70. Herre J, Gronlund H, Brooks H, et al. (2013). Allergens as immunomodulatory proteins: the cat dander protein Fel d 1 enhances TLR activation by lipid ligands. J Immunol 191: 1529-35
71. Hidaka F, Matsuo S, Muta T, et al. (2006). A missense mutation of the Toll-like receptor 3 gene in a patient with influenza-associated encephalopathy. Clin Immunol 119: 188-94
72. Higashikuni Y, Tanaka K, Kato M, et al. (2013). Toll-like receptor-2 mediates adaptive cardiac hypertrophy in response to pressure overload through interleukin-1beta upregulation via nuclear factor kappaB activation. J Am Heart Assoc 2: e000267
73. Hocking AM, Shinomura T, Mcquillan DJ. (1998). Leucine-rich repeat glycoproteins of the extracellular matrix. Matrix Biol 17: 1-19
74. Hodgkinson CP, Patel K, Ye S. (2008). Functional Toll-like receptor 4 mutations modulate the response to fibrinogen. Thromb Haemost 100: 301-7
75. Horak F. (2011). VTX-1463, a novel TLR8 agonist for the treatment of allergic rhinitis. Expert Opin Invest Drugs 20: 981-6
76. Hsieh LT, Nastase MV, Zeng-Brouwers J, et al. (2014). Soluble biglycan as a biomarker of inflammatory renal diseases. Int J Biochem Cell Biol 54: 223-35
77. Huang J, Xie Y, Sun X, et al. (2014). DAMPs, ageing, and cancer: the DAMP Hypothesis'. Ageing Res Rev. [Epub ahead of print]. doi: 10.1016/j.arr.2014.10.004
78. Huh JW, Shibata T, Hwang M, et al. (2014). UNC93B1 is essential for the plasma membrane localization and signaling of Toll-like receptor 5. Proc Natl Acad Sci USA 111: 7072-7
79. Ibrahim ZA, Armour CL, Phipps S, Sukkar MB. (2013). RAGE and TLRs: relatives, friends or neighbours? Mol Immunol 56: 739-44
80. Inohara N, Nunez G. (2002). ML-a conserved domain involved in innate immunity and lipid metabolism. Trends Biochem Sci 27: 219-21
81. Iozzo RV, Schaefer L. (2010). Proteoglycans in health and disease: novel regulatory signaling mechanisms evoked by the small leucine-rich proteoglycans. FEBS J 277: 3864-75
82. Ishii N, Funami K, Tatematsu M, et al. (2014). Endosomal localization of TLR8 confers distinctive proteolytic processing on human myeloid cells. J Immunol 193: 5118-28
83. Itoh H, Tatematsu M, Watanabe A, et al. (2011). UNC93B1 physically associates with human TLR8 and regulates TLR8-mediated signaling. PLoS One 6: e28500
84. Ivanov S, Dragoi AM, Wang X, et al. (2007). A novel role for HMGB1 in TLR9-mediated inflammatory responses to CpG-DNA. Blood 110: 1970-81
85. Ivicak-Kocjan K, Panter G, Bencina M, Jerala R. (2013). Determination of the physiological 2:2 TLR5:flagellin activation stoichiometry revealed by the activity of a fusion receptor. Biochem Biophys Res Commun 435: 40-5
86. Jahanyar J, Joyce DL, Southard RE, et al. (2007). Decorin-mediated transforming growth factor-beta inhibition ameliorates adverse cardiac remodeling. J Heart Lung Transplant 26: 34-40
87. Jelinek I, Leonard JN, Price GE, et al. (2011). TLR3-specific double-stranded RNA oligonucleotide adjuvants induce dendritic cell cross-presentation, CTL responses, and antiviral protection. J Immunol 186: 2422-9
88. Jin MS, Kim SE, Heo JY, et al. (2007). Crystal structure of the TLR1-TLR2 heterodimer induced by binding of a tri-acylated lipopeptide. Cell 130: 1071-82
89. Kaiser L, Gronlund H, Sandalova T, et al. (2003). The crystal structure of the major cat allergen Fel d 1, a member of the secretoglobin family. J Biol Chem 278: 37730-5
90. Kang JY, Nan X, Jin MS, et al. (2009). Recognition of lipopeptide patterns by Toll-like receptor 2-Toll-like receptor 6 heterodimer. Immunity 31: 873-84
91. Kang R, Chen R, Zhang Q, et al. (2014). HMGB1 in health and disease. Mol Aspects Med 40C: 1-116
92. Kanno A, Yamamoto C, Onji M, et al. (2013). Essential role for Toll-like receptor 7 (TLR7)-unique cysteines in an intramolecular disulfide bond, proteolytic cleavage and RNA sensing. Int Immunol 25: 413-22
93. Kariko K, Bhuyan P, Capodici J, et al. (2004a). Exogenous siRNA mediates sequence-independent gene suppression by signaling through Toll-like receptor 3. Cells Tissues Organs 177: 132-8
94. Kariko K, Ni H, Capodici J, et al. (2004b). mRNA is an endogenous ligand for Toll-like receptor 3. J Biol Chem 279: 12542-50
95. Kelsh RM, Mckeown-Longo PJ. (2013). Topographical changes in extracellular matrix: activation of TLR4 signaling and solid tumor progression. Trends Cancer Res 9: 1-13
96. Kelsh R, You R, Horzempa C, et al. (2014). Regulation of the innate immune response by fibronectin: synergism between the III-1 and EDA domains. PLoS One 9: e102974
97. Kim YM, Brinkmann MM, Paquet ME, Ploegh HL. (2008). UNC93B1 delivers nucleotide-sensing Toll-like receptors to endolysosomes. Nature 452: 234-8
98. Kim JY, Choung S, Lee EJ, et al. (2007). Immune activation by siRNA/liposome complexes in mice is sequence-independent: lack of a role for Toll-like receptor 3 signaling. Mol Cells 24: 247-54
99. Kormann MS, Depner M, Hartl D, et al. (2008). Toll-like receptor heterodimer variants protect from childhood asthma. J Allergy Clin Immunol 122: 86-92,. 92e1-8
100. Krieg AM, Yi AK, Matson S, et al. (1995). CpG motifs in bacterial DNA trigger direct B-cell activation. Nature 374: 546-9
101. Krug A, Luker GD, Barchet W, et al. (2004). Herpes simplex virus type 1 activates murine natural interferon-producing cells through Toll-like receptor 9. Blood 103: 1433-7
102. Kuhns DB, Priel DA, Gallin JI. (2007). Induction of human monocyte interleukin (IL)-8 by fibrinogen through the Toll-like receptor pathway. Inflammation 30: 178-88
103. Kulka M, Metcalfe DD. (2006). TLR3 activation inhibits human mast cell attachment to fibronectin and vitronectin. Mol Immunol 43: 1579-86
104. Kuriyama N, Duarte S, Hamada T, et al. (2011). Tenascin-C: a novel mediator of hepatic ischemia and reperfusion injury. Hepatology 54: 2125-36
105. Lande R, Gregorio J, Facchinetti V, et al. (2007). Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide. Nature 449: 564-9
106. Lasarte JJ, Casares N, Gorraiz M, et al. (2007). The extra domain A from fibronectin targets antigens to TLR4-expressing cells and induces cytotoxic T cell responses in vivo. J Immunol 178: 748-56
107. Latz E, Schoenemeyer A, Visintin A, et al. (2004). TLR9 signals after translocating from the ER to CpG DNA in the lysosome. Nat Immunol 5: 190-8
108. Latz E, Verma A, Visintin A, et al. (2007). Ligand-induced conformational changes allosterically activate Toll-like receptor 9. Nat Immunol 8: 772-9
109. Lee J, Chuang TH, Redecke V, et al. (2003). Molecular basis for the immunostimulatory activity of guanine nucleoside analogs: activation of Toll-like receptor 7. Proc Natl Acad Sci USA 100: 6646-51
110. Lee HK, Dunzendorfer S, Soldau K, Tobias PS. (2006). Double-stranded RNA-mediated TLR3 activation is enhanced by CD14. Immunity 24: 153-63
111. Lee BL, Moon JE, Shu JH, et al. (2013). UNC93B1 mediates differential trafficking of endosomal TLRs. Elife 2: e00291
112. Lefebvre JS, Levesque T, Picard S, et al. (2011). Extra domain A of fibronectin primes leukotriene biosynthesis and stimulates neutrophil migration through activation of Toll-like receptor 4. Arthritis Rheum 63: 1527-33
113. Lehmann SM, Kruger C, Park B, et al. (2012). An unconventional role for miRNA: let-7 activates Toll-like receptor 7 and causes neurodegeneration. Nat Neurosci 15: 827-35
114. Leonard JN, Ghirlando R, Askins J, et al. (2008). The TLR3 signaling complex forms by cooperative receptor dimerization. Proc Natl Acad Sci USA 105: 258-63
115. Li Y, Berke IC, Modis Y. (2012). DNA binding to proteolytically activated TLR9 is sequence-independent and enhanced by DNA curvature. EMBO J 31: 919-31
116. Li DQ, Zhang L, Pflugfelder SC, et al. (2011). Short ragweed pollen triggers allergic inflammation through Toll-like receptor 4-dependent thymic stromal lymphopoietin/OX40 ligand/OX40 signaling pathways. J Allergy Clin Immunol 128: 1318-25
117. Liu L, Botos I, Wang Y, et al. (2008). Structural basis of Toll-like receptor 3 signaling with double-stranded RNA. Science 320: 379-81
118. Liu R, He Y, Li B, et al. (2012). Tenascin-C produced by oxidized LDL-stimulated macrophages increases foam cell formation through Toll-like receptor-4. Mol Cells 34: 35-41
119. Liu B, Yang Y, Qiu Z, et al. (2010). Folding of Toll-like receptors by the HSP90 paralogue gp96 requires a substrate-specific cochaperone. Nat Commun 1: 79
120. Lonez C, Irvine K, Pizzuto M, et al. (2014). Novel mechanism of TLR4 activation by cationic lipids. eLife 15:R111
121. Lorenz W, Buhrmann C, Mobasheri A, et al. (2013). Bacterial lipopolysaccharides form procollagen-endotoxin complexes that trigger cartilage inflammation and degeneration: implications for the development of rheumatoid arthritis. Arthritis Res Ther 15: R111
122. Lund JM, Alexopoulou L, Sato A, et al. (2004). Recognition of single-stranded RNA viruses by Toll-like receptor 7. Proc Natl Acad Sci USA 101: 5598-603
123. Magna M, Pisetsky DS. (2014). The role of HMGB1 in the pathogenesis of inflammatory and autoimmune diseases. Mol Med 20: 138-46
124. Maisonneuve C, Bertholet S, Philpott DJ, De Gregorio E. (2014). Unleashing the potential of NOD- and Toll-like agonists as vaccine adjuvants. Proc Natl Acad Sci USA 111: 12294-9
125. Martinez FD. (2007). CD14, endotoxin, and asthma risk: actions and interactions. Proc Am Thorac Soc 4: 221-5
126. Matijevic T, Pavelic J. (2011). The dual role of TLR3 in metastatic cell line. Clin Exp Metastasis 28: 701-12
127. Mcilroy G, Foldi I, Aurikko J, et al. (2013). Toll-6 and Toll-7 function as neurotrophin receptors in the Drosophila melanogaster CNS. Nat Neurosci 16: 1248-56
128. Medeiros DM, Velleman SG, Jarrold BB, et al. (2002). Ontogeny of enhanced decorin levels and distribution within myocardium of failing hearts. Connect Tissue Res 43: 32-43
129. Meirovitz A, Goldberg R, Binder A, et al. (2013). Heparanase in inflammation and inflammation-associated cancer. FEBS J 280: 2307-19
130. Meng J, Lien E, Golenbock DT. (2009). MD-2-mediated ionic interactions between lipid A and TLR4 are essential for receptor activation. J Biol Chem 285: 8695-702
131. Merline R, Lazaroski S, Babelova A, et al. (2009a). Decorin deficiency in diabetic mice: aggravation of nephropathy due to overexpression of profibrotic factors, enhanced apoptosis and mononuclear cell infiltration. J Physiol Pharmacol 60: 5-13
132. Merline R, Moreth K, Beckmann J, et al. (2011). Signaling by the matrix proteoglycan decorin controls inflammation and cancer through PDCD4 and MicroRNA-21. Sci Signal 4: ra75
133. Merline R, Schaefer RM, Schaefer L. (2009b). The matricellular functions of small leucine-rich proteoglycans (SLRPs). J Cell Commun Signal 3: 323-35
134. Mickiene A, Pakalniene J, Nordgren J, et al. (2014). Polymorphisms in chemokine receptor 5 and Toll-like receptor 3 genes are risk factors for clinical tick-borne encephalitis in the lithuanian population. PLoS One 9: e106798
135. Midwood K, Sacre S, Piccinini AM, et al. (2009a). Tenascin-C is an endogenous activator of Toll-like receptor 4 that is essential for maintaining inflammation in arthritic joint disease. Nat Med 15: 774-80
136. Midwood KS, Piccinini AM, Sacre, S. (2009b). Targeting Toll-like receptors in autoimmunity. Curr Drug Targets 10: 1139-55
137. Millien VO, Lu W, Shaw J, et al. (2013). Cleavage of fibrinogen by proteinases elicits allergic responses through Toll-like receptor 4. Science 341: 792-6
138. Mogami H, Keller PW, Shi H, Word RA. (2014). Effect of thrombin on human amnion mesenchymal cells, mouse fetal membranes, and preterm birth. J Biol Chem 289: 13295-307
139. Monick MM, Powers L, Butler N, et al. (2002). Interaction of matrix with integrin receptors is required for optimal LPS-induced MAP kinase activation. Am J Physiol Lung Cell Mol Physiol 283: L390-402
140. Moreth K, Brodbeck R, Babelova A, et al. (2010). The proteoglycan biglycan regulates expression of the B cell chemoattractant CXCL13 and aggravates murine lupus nephritis. J Clin Invest 120: 4251-72
141. Moreth K, Frey H, Hubo M, et al. (2014). Biglycan-triggered TLR-2- and TLR-4-signaling exacerbates the pathophysiology of ischemic acute kidney injury. Matrix Biol 35: 143-51
142. Moreth K, Iozzo RV, Schaefer L. (2012). Small leucine-rich proteoglycans orchestrate receptor crosstalk during inflammation. Cell Cycle 11: 2084-91
143. Motojima M, Matsusaka T, Kon V, Ichikawa I. (2010). Fibrinogen that appears in Bowman's space of proteinuric kidneys in vivo activates podocyte Toll-like receptors 2 and 4 in vitro. Nephron Exp Nephrol 114: e39-47
144. Murakami Y, Fukui R, Motoi Y, et al. (2014). Roles of the cleaved N-terminal TLR3 fragment and cell surface TLR3 in double-strand RNA sensing. J Immunol 193: 5208-17
145. Nagai Y, Akashi S, Nagafuku M, et al. (2002a). Essential role of MD-2 in LPS responsiveness and TLR4 distribution. Nat Immunol 3: 667-72
146. Nagai Y, Shimazu R, Ogata H, et al. (2002b). Requirement for MD-1 in cell surface expression of RP105/CD180 and B-cell responsiveness to lipopolysaccharide. Blood 99: 1699-705
147. Nastase MV, Iozzo RV, Schaefer L. (2014). Key roles for the small leucine-rich proteoglycans in renal and pulmonary pathophysiology. Biochim Biophys Acta 1840: 2460-70
148. Nastase MV, Young MF, Schaefer L. (2012). Biglycan: a multivalent proteoglycan providing structure and signals. J Histochem Cytochem 60: 963-75
149. Neill T, Schaefer L, Iozzo RV. (2012). Decorin: a guardian from the matrix. Am J Pathol 181: 380-7
150. Oh DY, Taube S, Hamouda O, et al. (2008). A functional Toll-like receptor 8 variant is associated with HIV disease restriction. J Infect Dis 198: 701-9
151. Okahira S, Nishikawa F, Nishikawa S, et al. (2005). Interferon-beta induction through Toll-like receptor 3 depends on double-stranded RNA structure. DNA Cell Biol 24: 614-23
152. Okamura Y, Watari M, Jerud ES, et al. (2001). The extra domain A of fibronectin activates Toll-like receptor 4. J Biol Chem 276: 10229-33
153. O'Neill LA, Bryant CE, Doyle SL. (2009). Therapeutic targeting of Toll-like receptors for infectious and inflammatory diseases and cancer. Pharmacol Rev 61: 177-97
154. Onji M, Kanno A, Saitoh S, et al. (2013). An essential role for the N-terminal fragment of Toll-like receptor 9 in DNA sensing. Nat Commun 4: 1949. doi: 10.1038/ncomms2949
155. Pal D, Dasgupta S, Kundu R, et al. (2012). Fetuin-A acts as an endogenous ligand of TLR4 to promote lipid-induced insulin resistance. Nat Med 18: 1279-85
156. Park B, Brinkmann MM, Spooner E, et al. (2008). Proteolytic cleavage in an endolysosomal compartment is required for activation of Toll-like receptor 9. Nat Immunol 9: 1407-14
157. Park B, Buti L, Lee S, et al. (2011). Granulin is a soluble cofactor for Toll-like receptor 9 signaling. Immunity 34: 505-13
158. Park BS, Song DH, Kim HM, et al. (2009). The structural basis of lipopolysaccharide recognition by the TLR4-MD-2 complex. Nature 458: 1191-5
159. Patel L, Sun W, Glasson SS, et al. (2011). Tenascin-C induces inflammatory mediators and matrix degradation in osteoarthritic cartilage. BMC Musculoskelet Disord 12: 164
160. Pelka K, Phulphagar K, Zimmermann J, et al. (2014). Cutting Edge: the UNC93B1 tyrosine-based motif regulates trafficking and TLR responses via separate mechanisms. J Immunol 193: 3257-61
161. Petretto E, Sarwar R, Grieve I, et al. (2008). Integrated genomic approaches implicate osteoglycin (Ogn) in the regulation of left ventricular mass. Nat Genet 40: 546-52
162. Petrey AC, De La Motte CA. (2014). Hyaluronan, a crucial regulator of inflammation. Front Immunol 5: 101. doi: 10.3389/fimmu.2014.00101
163. Piccinini AM, Midwood KS. (2010). DAMPening inflammation by modulating TLR signalling. Mediators Inflamm 2010: 672395. doi: 10.1155/2010/672395
164. Piccinini AM, Midwood KS. (2012). Endogenous control of immunity against infection: tenascin-C regulates TLR4-mediated inflammation via microRNA-155. Cell Rep 2: 914-26
165. Pohar J, Pirher N, Bencina M, et al. (2013). The role of UNC93B1 protein in surface localization of TLR3 receptor and in cell priming to nucleic acid agonists. J Biol Chem 288: 442-54
166. Popa C, Van Lieshout AW, Roelofs MF, et al. (2006). MIF production by dendritic cells is differentially regulated by Toll-like receptors and increased during rheumatoid arthritis. Cytokine 36: 51-6
167. Popovic ZV, Wang S, Papatriantafyllou M, et al. (2011). The proteoglycan biglycan enhances antigen-specific T cell activation potentially via MyD88 and TRIF pathways and triggers autoimmune perimyocarditis. J Immunol 187: 6217-26
168. Raby AC, Holst B, Le Bouder E, et al. (2013). Targeting the TLR co-receptor CD14 with TLR2-derived peptides modulates immune responses to pathogens. Sci Transl Med 5: 185ra64
169. Raghavan B, Martin SF, Esser PR, et al. (2012). Metal allergens nickel and cobalt facilitate TLR4 homodimerization independently of MD2. EMBO Rep 13: 1109-15
170. Resman N, Vasl J, Oblak A, et al. (2009). Essential roles of hydrophobic residues in both MD-2 and toll-like receptor 4 in activation by endotoxin. J Biol Chem 284:15052-60
171. Ribes S, Ebert S, Regen T, et al. (2010). Fibronectin stimulates Escherichia coli phagocytosis by microglial cells. Glia 58: 367-76
172. Rigby RE, Webb LM, Mackenzie KJ, et al. (2014). RNA:DNA hybrids are a novel molecular pattern sensed by TLR9. EMBO J 33: 542-58
173. Roberts BJ, Moussawi M, Huber SA. (2013). Sex differences in TLR2 and TLR4 expression and their effect on coxsackievirus-induced autoimmune myocarditis. Exp Mol Pathol 94: 58-64
174. Rock FL, Hardiman G, Timans JC, et al. (1998). A family of human receptors structurally related to Drosophila Toll. Proc Natl Acad Sci USA 95: 588-93
175. Roelofs MF, Abdollahi-Roodsaz S, Joosten LA, et al. (2008). The orchestra of Toll-like receptors and their potential role in frequently occurring rheumatic conditions. Arthritis Rheum 58: 338-48
176. Ross MA, Curtis L, Scheff PA, et al. (2000). Association of asthma symptoms and severity with indoor bioaerosols. Allergy 55: 705-11
177. Rudd BD, Burstein E, Duckett CS, et al. (2005). Differential role for TLR3 in respiratory syncytial virus-induced chemokine expression. J Virol 79: 3350-7
178. Ruppert SM, Hawn TR, Arrigoni A, et al. (2014). Tissue integrity signals communicated by high-molecular weight hyaluronan and the resolution of inflammation. Immunol Res 58: 186-92
179. Rutz M, Metzger J, Gellert T, et al. (2004). Toll-like receptor 9 binds single-stranded CpG-DNA in a sequence- and pH-dependent manner. Eur J Immunol 34: 2541-50
180. Ryu JH, Yoo JY, Kim MJ, et al. (2013). Distinct TLR-mediated pathways regulate house dust mite-induced allergic disease in the upper and lower airways. J Allergy Clin Immunol 131: 549-61
181. Sakata Y, Dong JW, Vallejo JG, et al. (2007). Toll-like receptor 2 modulates left ventricular function following ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol 292: H503-9
182. Sasai M, Linehan MM, Iwasaki A. (2010). Bifurcation of Toll-like receptor 9 signaling by adaptor protein 3. Science 329: 1530-4
183. Satoh M, Shimoda Y, Maesawa C, et al. (2006). Activated Toll-like receptor 4 in monocytes is associated with heart failure after acute myocardial infarction. Int J Cardiol 109: 226-34
184. Savarese E, Chae OW, Trowitzsch S, et al. (2006). U1 small nuclear ribonucleoprotein immune complexes induce type I interferon in plasmacytoid dendritic cells through TLR7. Blood 107: 3229-34
185. Schaefer L. (2014). Complexity of danger: the diverse nature of damage-associated molecular patterns. J Biol Chem 289:35237-45
186. Schaefer L, Babelova A, Kiss E, et al. (2005). The matrix component biglycan is proinflammatory and signals through Toll-like receptors 4 and 2 in macrophages. J Clin Invest 115: 2223-33
187. Schaefer L, Iozzo RV. (2008). Biological functions of the small leucine-rich proteoglycans: from genetics to signal transduction. J Biol Chem 283: 21305-9
188. Schaefer L, Iozzo RV. (2012). Small leucine-rich proteoglycans, at the crossroad of cancer growth and inflammation. Curr Opin Genet Dev 22: 56-7
189. Schaefer L, Macakova K, Raslik I, et al. (2002). Absence of decorin adversely influences tubulointerstitial fibrosis of the obstructed kidney by enhanced apoptosis and increased inflammatory reaction. Am J Pathol 160: 1181-91
190. Schaefer L, Raslik I, Grone HJ, et al. (2001). Small proteoglycans in human diabetic nephropathy: discrepancy between glomerular expression and protein accumulation of decorin, biglycan, lumican, and fibromodulin. FASEB J 15: 559-61
191. Schmidt M, Raghavan B, Muller V, et al. (2010). Crucial role for human Toll-like receptor 4 in the development of contact allergy to nickel. Nat Immunol 11: 814-19
192. Shishido T, Nozaki N, Yamaguchi S, et al. (2003). Toll-like receptor-2 modulates ventricular remodeling after myocardial infarction. Circulation 108: 2905-10
193. Smiley ST, King JA, Hancock WW. (2001). Fibrinogen stimulates macrophage chemokine secretion through Toll-like receptor 4. J Immunol 167: 2887-94
194. Sokolove J, Zhao X, Chandra PE, Robinson WH. (2011). Immune complexes containing citrullinated fibrinogen costimulate macrophages via Toll-like receptor 4 and Fcgamma receptor. Arthritis Rheum 63: 53-62
195. Sorensen I, Susnik N, Inhester T, et al. (2011). Fibrinogen, acting as a mitogen for tubulointerstitial fibroblasts, promotes renal fibrosis. Kidney Int 80: 1035-44
196. Spitzauer S. (1999). Allergy to mammalian proteins: at the borderline between foreign and self? Int Arch Allergy Immunol 120: 259-69
197. Suwarti S, Yamazaki T, Svetlana C, Hanagata N. (2013). Recognition of CpG oligodeoxynucleotides by human Toll-like receptor 9 and subsequent cytokine induction. Biochem Biophys Res Commun 430: 1234-9
198. Takahashi K, Shibata T, Akashi-Takamura S, et al. (2007). A protein associated with Toll-like receptor (TLR) 4 (PRAT4A) is required for TLR-dependent immune responses. J Exp Med 204: 2963-76
199. Tang D, Kang R, Coyne CB, et al. (2012). PAMPs and DAMPs: signal 0s that spur autophagy and immunity. Immunol Rev 249: 158-75
200. Tanji H, Ohto U, Shibata T, et al. (2013). Structural reorganization of the Toll-like receptor 8 dimer induced by agonistic ligands. Science 339: 1426-9
201. Tatematsu M, Nishikawa F, Seya T, Matsumoto M. (2013). Toll-like receptor 3 recognizes incomplete stem structures in single-stranded viral RNA. Nat Commun 4: 1833. doi: 10.1038/ncomms2857
202. Telepnev MV, Klimpel GR, Haithcoat J, et al. (2009). Tetraacylated lipopolysaccharide of Yersinia pestis can inhibit multiple Toll-like receptor-mediated signaling pathways in human dendritic cells. J Infect Dis 200: 1694-702
203. Timmers L, Sluijter JP, Van Keulen JK, et al. (2008). Toll-like receptor 4 mediates maladaptive left ventricular remodeling and impairs cardiac function after myocardial infarction. Circ Res 102: 257-64
204. To WS, Midwood KS. (2011). Plasma and cellular fibronectin: distinct and independent functions during tissue repair. Fibrogenesis Tissue Repair 4: 21. doi: 10.1186/1755-1536-4-21
205. Trompette A, Divanovic S, Visintin A, et al. (2009). Allergenicity resulting from functional mimicry of a Toll-like receptor complex protein. Nature 457: 585-8
206. Tsan MF, Gao B. (2009). Heat shock proteins and immune system. J Leukoc Biol 85: 905-10
207. Tsui FW, Xi N, Rohekar S, et al. (2008). Toll-like receptor 2 variants are associated with acute reactive arthritis. Arthritis Rheum 58: 3436-8
208. Udalova IA, Ruhmann M, Thomson SJ, Midwood KS. (2011). Expression and immune function of tenascin-C. Crit Rev Immunol 31: 115-45
209. Vacchelli E, Eggermont A, Sautes-Fridman C, et al. (2013). Trial Watch: Toll-like receptor agonists for cancer therapy. Oncoimmunology 2: e25238
210. Vanhoutte D, Van Almen GC, Van Aelst LN, et al. (2013). Matricellular proteins and matrix metalloproteinases mark the inflammatory and fibrotic response in human cardiac allograft rejection. Eur Heart J 34: 1930-41
211. Viglianti GA, Lau CM, Hanley TM, et al. (2003). Activation of autoreactive B cells by CpG dsDNA. Immunity 19: 837-47
212. Wakabayashi Y, Kobayashi M, Akashi-Takamura S, et al. (2006). A protein associated with Toll-like receptor 4 (PRAT4A) regulates cell surface expression of TLR4. J Immunol 177: 1772-9
213. Walsh C, Gangloff M, Monie T, et al. (2008). Elucidation of the MD-2/TLR4 interface required for signaling by lipid IVa. J Immunol 181: 1245-54
214. Wang T, Town T, Alexopoulou L, et al. (2004). Toll-like receptor 3 mediates West Nile virus entry into the brain causing lethal encephalitis. Nat Med 10: 1366-73
215. Weber A, Tauszig-Delamasure S, Hoffmann J, et al. (2003). Binding of the Drosophila cytokine Spätzle to Toll is direct and establishes signaling. Nat Immunol 4: 794-800
216. Weber C, Muller C, Podszuweit A, et al. (2012). Toll-like receptor (TLR) 3 immune modulation by unformulated small interfering RNA or DNA and the role of CD14 (in TLR-mediated effects). Immunology 136: 64-77
217. Wiertsema SP, Khoo SK, Baynam G, et al. (2006). Association of CD14 promoter polymorphism with otitis media and pneumococcal vaccine responses. Clin Vaccine Immunol 13: 892-7
218. Williams KJ, Qiu G, Usui HK, et al. (2007). Decorin deficiency enhances progressive nephropathy in diabetic mice. Am J Pathol 171: 1441-50
219. Wilson RH, Maruoka S, Whitehead GS, et al. (2012). The Toll-like receptor 5 ligand flagellin promotes asthma by priming allergic responses to indoor allergens. Nat Med 18: 1705-10
220. Wolberg AS. (2012). Determinants of fibrin formation, structure, and function. Curr Opin Hematol 19: 349-56
221. Wu F, Vij N, Roberts L, et al. (2007). A novel role of the lumican core protein in bacterial lipopolysaccharide-induced innate immune response. J Biol Chem 282: 26409-17
222. Yamaguchi Y, Mann DM, Ruoslahti E. (1990). Negative regulation of transforming growth factor-beta by the proteoglycan decorin. Nature 346: 281-4
223. Yan W, Wang P, Zhao CX, et al. (2009). Decorin gene delivery inhibits cardiac fibrosis in spontaneously hypertensive rats by modulation of transforming growth factor-beta/Smad and p38 mitogen-activated protein kinase signaling pathways. Hum Gene Ther 20: 1190-200
224. Yanai H, Ban T, Wang Z, et al. (2009). HMGB proteins function as universal sentinels for nucleic-acid-mediated innate immune responses. Nature 462: 99-103
225. Yang Y, Liu B, Dai J, et al. (2007). Heat shock protein gp96 is a master chaperone for Toll-like receptors and is important in the innate function of macrophages. Immunity 26: 215-26
226. Yoon SI, Kurnasov O, Natarajan V, et al. (2012). Structural basis of TLR5-flagellin recognition and signaling. Science 335: 859-64
227. Yoshida H, Nishikawa M, Yasuda S, et al. (2012). Fibronectin inhibits cytokine production induced by CpG DNA in macrophages without direct binding to DNA. Cytokine 60: 162-70
228. You R, Zheng M, Mckeown-Longo PJ. (2010). The first type III repeat in fibronectin activates an inflammatory pathway in dermal fibroblasts. J Biol Chem 285: 36255-9
229. Yu L, Wang L, Chen S. (2010). Endogenous Toll-like receptor ligands and their biological significance. J Cell Mol Med 14: 2592-603
230. Zanin-Zhorov A, Tal-Lapidot G, Cahalon L, et al. (2007). Cutting edge: T cells respond to lipopolysaccharide innately via TLR4 signaling. J Immunol 179: 41-4
231. Zeng-Brouwers J, Beckmann J, Nastase MV, et al. (2014). De novo expression of circulating biglycan evokes an innate inflammatory tissue response via MyD88/TRIF pathways. Matrix Biol 35: 132-42
232. Zhang SY, Jouanguy E, Ugolini S, et al. (2007). TLR3 deficiency in patients with herpes simplex encephalitis. Science 317: 1522-7
233. Zheng M, Jones DM, Horzempa C, et al. (2011). The first type III domain of fibronectin is associated with the expression of cytokines within the lung tumor microenvironment. J Cancer 2: 478-83
234. Zhu J, Huang X, Yang Y. (2007). Innate immune response to adenoviral vectors is mediated by both Toll-like receptor-dependent and -independent pathways. J Virol 81: 3170-80
235. Zhu Q, Zou L, Jagavelu K, et al. (2012). Intestinal decontamination inhibits TLR4 dependent fibronectin-mediated cross-talk between stellate cells and endothelial cells in liver fibrosis in mice. J Hepatol 56: 893-9
236. Zimmerman SD, Thomas DP, Velleman SG, et al. (2001). Time course of collagen and decorin changes in rat cardiac and skeletal muscle post-MI. Am J Physiol Heart Circ Physiol 281: H1816-22