Translational mini-review series on Toll-like receptors: Toll-like receptor ligands as novel pharmaceuticals for allergic disorders

Clinical and Experimental Immunology

Volumn 147, Issue 2, 2007, Pages 208-216

  Goldman, M ^a,b  

^a UNIVERSITÉ LIBRE DE BRUXELLES   (Belgium)

^b Institute for Medical Immunology   (Belgium)

Author keywords

Allergy; Hygiene; Immunotherapy; Inflammation; Toll like receptor

Indexed keywords

BACTERIUM LIPOPOLYSACCHARIDE; TOLL LIKE RECEPTOR; TOLL LIKE RECEPTOR 2; TOLL LIKE RECEPTOR 4; TOLL LIKE RECEPTOR 7; TOLL LIKE RECEPTOR 9;

ADAPTIVE IMMUNITY; ALLERGIC DISEASE; ALLERGIC REACTION; ATOPY; CYTOKINE PRODUCTION; DISEASE PREDISPOSITION; DRUG MEGADOSE; EFFECTOR CELL; EPITHELIUM CELL; HUMAN; IMMUNE MEDIATED INJURY; IMMUNOTHERAPY; INNATE IMMUNITY; LOW DRUG DOSE; LYMPHOCYTE ACTIVATION; MAST CELL; NONHUMAN; PRIORITY JOURNAL; SHORT SURVEY;

ANTI-ALLERGIC AGENTS; DENDRITIC CELLS; HUMANS; HYGIENE; HYPERSENSITIVITY; IMMUNOTHERAPY; LIGANDS; T-LYMPHOCYTES, REGULATORY; TOLL-LIKE RECEPTORS;

EID: 33846213140     PISSN: 00099104     EISSN: 13652249     Source Type: Journal    
DOI: 10.1111/j.1365-2249.2006.03296.x     Document Type: Short Survey

References (119)

1. Strachan DP. Hay fever, hygiene, and household size. BMJ 1989;299:1259-60.
2. Marks GB. Environmental factors and gene-environment interactions in the aetiology of asthma. Clin Exp Pharmacol Physiol 2006;33:285-9.
3. Braun-Fahrlander C, Riedler J, Herz U et al. Environmental exposure to endotoxin and its relation to asthma in school-age children. N Engl J Med 2002; 347:869-77.
4. Martinez FD, Holt PG. Role of microbial burden in aetiology of allergy and asthma. Lancet 1999; 354 (Suppl. 2):SII12-5.
5. Shirakawa T, Enomoto T, Shimazu S, Hopkin JM. The inverse association between tuberculin responses and atopic disorder. Science 1997; 275:77-9.
6. Wills-Karp M, Santeliz J, Karp CL. The germless theory of allergic disease: revisiting the hygiene hypothesis. Nat Rev Immunol 2001; 1:69-75.
7. Yazdanbakhsh M, Kremsner PG, van Ree R. Allergy, parasites, and the hygiene hypothesis. Science 2002; 296:490-4.
8. Aaby P, Shaheen SO, Heyes CB et al. Early BCG vaccination and reduction in atopy in Guinea-Bissau. Clin Exp Allergy 2000; 30:644-50.
9. Alm JS, Lilja G, Pershagen G, Scheynius A. Early BCG vaccination and development of atopy. Lancet 1997; 350:400-3.
10. Marks GB, Ng K, Zhou J et al. The effect of neonatal BCG vaccination on atopy and asthma at age 7-14 years: an historical cohort study in a community with a very low prevalence of tuberculosis infection and a high prevalence of atopic disease. J Allergy Clin Immunol 2003; 111:541-9.
11. Li R, Yang X, Wang L, Liu E. Respiratory syncytial virus infection reversed anti-asthma effect of neonatal bacillus Calmette-Guerin vaccination in BALB/c mice. Pediatr Res 2006; 59:210-5.
12. Gereda JE, Leung DY, Thatayatikom A et al. Relation between house-dust endotoxin exposure, type 1 T-cell development, and allergen sensitisation in infants at high risk of asthma. Lancet 2000; 355:1680-3.
13. Michel O, Kips J, Duchateau J et al. Severity of asthma is related to endotoxin in house dust. Am J Respir Crit Care Med 1996; 154:1641-6.
14. Tavernier G, Fletcher G, Gee I et al. IPEADAM study: indoor endotoxin exposure, family status, and some housing characteristics in English children. J Allergy Clin Immunol 2006; 117:656-62.
15. Thorne PS, Kulhankova K, Yin M, Cohn R, Arbes SJ Jr, Zeldin DC. Endotoxin exposure is a risk factor for asthma: the national survey of endotoxin in United States housing. Am J Respir Crit Care Med 2005; 172:1371-7.
16. Tulic MK, Wale JL, Holt PG, Sly PD. Modification of the inflammatory response to allergen challenge after exposure to bacterial lipopolysaccharide. Am J Respir Cell Mol Biol 2000; 22:604-12.
17. Douwes J, van Strien R, Doekes G et al. Does early indoor microbial exposure reduce the risk of asthma? The Prevention and Incidence of Asthma and Mite Allergy birth cohort study. J Allergy Clin Immunol 2006; 117:1067-73.
18. Liu AH, Leung DY. Renaissance of the hygiene hypothesis. J Allergy Clin Immunol 2006; 117:1063-6.
19. Roy SR, Schiltz AM, Marotta A, Shen Y, Liu AH. Bacterial DNA in house and farm barn dust. J Allergy Clin Immunol 2003; 112:571-8.
20. van Strien RT, Engel R, Holst O et al. Microbial exposure of rural school children, as assessed by levels of N-acetyl-muramic acid in mattress dust, and its association with respiratory health. J Allergy Clin Immunol 2004; 113:860-7.
21. Maizels RM, Yazdanbakhsh M. Immune regulation by helminth parasites: cellular and molecular mechanisms. Nat Rev Immunol 2003; 3:733-44.
22. Takeda K, Akira S. Toll-like receptors in innate immunity. Int Immunol 2005; 17:1-14.
23. Pugin J, Heumann ID, Tomasz A et al. CD14 is a pattern recognition receptor. Immunity 1994; 1:509-16.
24. Werner M, Topp R, Wimmer K et al. TLR4 gene variants modify endotoxin effects on asthma. J Allergy Clin Immunol 2003; 112:323-30.
25. Yang IA, Barton SJ, Rorke S et al. Toll-like receptor 4 polymorphism and severity of atopy in asthmatics. Genes Immun 2004; 5:41-5.
26. Yang IA, Holgate ST, Holloway JW. Toll-like receptor polymorphisms and allergic disease: interpreting the evidence from genetic studies. Clin Exp Allergy 2004; 34:163-6.
27. Eder W, Klimecki W, Yu L et al. Toll-like receptor 2 as a major gene for asthma in children of European farmers. J Allergy Clin Immunol 2004; 113:482-8.
28. Lewis DB, Yu CC, Meyer J, English BK, Kahn SJ, Wilson CB. Cellular and molecular mechanisms for reduced interleukin 4 and interferon-gamma production by neonatal T cells. J Clin Invest 1991; 87:194-202.
29. Goriely S, Van Lint C, Dadkhah R et al. A defect in nucleosome remodeling prevents IL-12 (p35) gene transcription in neonatal dendritic cells. J Exp Med 2004; 199:1011-16.
30. Prescott SL, Taylor A, King B et al. Neonatal interleukin-12 capacity is associated with variations in allergen-specific immune responses in the neonatal and postnatal periods. Clin Exp Allergy 2003; 33:566-72.
31. van den Biggelaar AH, Rodrigues LC, van Ree R et al. Long-term treatment of intestinal helminths increases mite skin-test reactivity in Gabonese schoolchildren. J Infect Dis 2004; 189:892-900.
32. van den Biggelaar AH, van Ree R, Rodrigues LC et al. Decreased atopy in children infected with Schistosoma haematobium: a role for parasite-induced interleukin-10. Lancet 2000; 356:1723-7.
33. Bach JF. The effect of infections on susceptibility to autoimmune and allergic diseases. N Engl J Med 2002; 347:911-20.
34. Wilson MS, Taylor MD, Balic A, Finney CA, Lamb JR, Maizels RM. Suppression of allergic airway inflammation by helminth-induced regulatory T cells. J Exp Med 2005; 202:1199-212.
35. Chatila TA, Blaeser F, Ho N et al. JM2, encoding a fork head-related protein, is mutated in X-linked autoimmunity-allergic disregulation syndrome. J Clin Invest 2000; 106:R75-81.
36. Akdis M, Verhagen J, Taylor A et al. Immune responses in healthy and allergic individuals are characterized by a fine balance between allergen-specific T regulatory 1 and T helper 2 cells. J Exp Med 2004; 199:1567-75.
37. Ling EM, Smith T, Nguyen XD et al. Relation of CD4+CD25+ regulatory T-cell suppression of allergen-driven T-cell activation to atopic status and expression of allergic disease. Lancet 2004; 363:608-15.
38. Hawrylowicz CM, O'Garra A. Potential role of interleukin-10-secreting regulatory T cells in allergy and asthma. Nat Rev Immunol 2005; 5:271-83.
39. Zuany-Amorim C, Sawicka E, Manlius C et al. Suppression of airway eosinophilia by killed Mycobacterium vaccae-induced allergen-specific regulatory T-cells. Nat Med 2002; 8:625-9.
40. Kalliomaki M, Salminen S, Poussa T, Arvilommi H, Isolauri E. Probiotics and prevention of atopic disease: 4-year follow-up of a randomised placebo-controlled trial. Lancet 2003; 361:1869-71.
41. Arkwright PD, David TJ. Intradermal administration of a killed Mycobacterium vaccae suspension (SRL 172) is associated with improvement in atopic dermatitis in children with moderate-to-severe disease. J Allergy Clin Immunol 2001; 107:531-4.
42. Feleszko W, Jaworska J, Hamelmann E. Toll-like receptors - novel targets in allergic airway disease (probiotics, friends and relatives). Eur J Pharmacol 2006; 533:308-18.
43. Purkerson JM, Isakson PC. Independent regulation of DNA recombination and immunoglobulin (Ig) secretion during isotype switching to IgG1 and IgE. J Exp Med 1994; 179:1877-83.
44. Eisenbarth SC, Piggott DA, Huleatt JW, Visintin I, Herrick CA, Bottomly K. Lipopolysaccharide-enhanced, toll-like receptor 4-dependent T helper cell type 2 responses to inhaled antigen. J Exp Med 2002; 196:1645-51.
45. Piggott DA, Eisenbarth SC, Xu L et al. MyD88-dependent induction of allergic Th2 responses to intranasal antigen. J Clin Invest 2005; 115:459-67.
46. Lundy SK, Berlin AA, Lukacs NW. Interleukin-12-independent down-modulation of cockroach antigen-induced asthma in mice by intranasal exposure to bacterial lipopolysaccharide. Am J Pathol 2003; 163:1961-8.
47. Kamath AV, Pavord ID, Ruparelia PR, Chilvers ER. Is the neutrophil the key effector cell in severe asthma? Thorax 2005; 60:529-30.
48. Michel O, Ginanni R, Le Bon B, Content J, Duchateau J, Sergysels R. Inflammatory response to acute inhalation of endotoxin in asthmatic patients. Am Rev Respir Dis 1992; 146:352-7.
49. Rodriguez D, Keller AC, Faquim-Mauro EL et al. Bacterial lipopolysaccharide signaling through Toll-like receptor 4 suppresses asthma-like responses via nitric oxide synthase 2 activity. J Immunol 2003; 171:1001-8.
50. Gerhold K, Bluemchen K, Franke A, Stock P, Hamelmann E. Exposure to endotoxin and allergen in early life and its effect on allergen sensitization in mice. J Allergy Clin Immunol 2003; 112:389-96.
51. Ng N, Lam D, Paulus P, Batzer G, Horner AA. House dust extracts have both TH2 adjuvant and tolerogenic activities. J Allergy Clin Immunol 2006; 117:1074-81.
52. Hollingsworth JW, Whitehead GS, Lin KL et al. TLR4 signaling attenuates ongoing allergic inflammation. J Immunol 2006; 176:5856-62.
53. Wang Y, McCusker C. Neonatal exposure with LPS and/or allergen prevents experimental allergic airways disease: development of tolerance using environmental antigens. J Allergy Clin Immunol 2006; 118:143-51.
54. Tulic MK, Fiset PO, Manoukian JJ et al. Role of Toll-like receptor 4 in protection by bacterial lipopolysaccharide in the nasalmucosa of atopic children but not adults. Lancet 2004; 363:1689-97.
55. Duez C, Gosset P, Tonnel AB. Dendritic cells and Toll-like receptors in allergy and asthma. Eur J Dermatol 2006; 16:12-6.
56. Eisenbarth SC, Piggott DA, Bottomly K. The master regulators of allergic inflammation: dendritic cells in Th2 sensitization. Curr Opin Immunol 2003; 15:620-6.
57. Amsen D, Blander JM, Lee GR, Tanigaki K, Honjo T, Flavell RA. Instruction of distinct CD4 T helper cell fates by different notch ligands on antigen-presenting cells. Cell 2004; 117:515-26.
58. Napolitani G, Rinaldi A, Bertoni F, Sallusto F, Lanzavecchia A. Selected Toll-like receptor agonist combinations synergistically trigger a T helper type 1-polarizing program in dendritic cells. Nat Immunol 2005; 6:769-76.
59. Caron G, Delneste Y, Roelandts E et al. Histamine polarizes human dendritic cells into Th2 cell-promoting effector dendritic cells. J Immunol 2001; 167:3682-6.
60. Liu YJ. Thymic stromal lymphopoietin: master switch for allergic inflammation. J Exp Med 2006; 203:269-73.
61. Weaver CT, Harrington LE, Mangan PR, Gavrieli M, Murphy KM. Th17: an effector CD4 T cell lineage with regulatory T cell ties. Immunity 2006; 24:677-88.
62. Molet S, Hamid Q, Davoine F et al. IL-17 is increased in asthmatic airways and induces human bronchial fibroblasts to produce cytokines. J Allergy Clin Immunol 2001; 108:430-8.
63. Rahman MS, Yamasaki A, Yang J, Shan L, Halayko AJ, Gounni AS. IL-17A Induces eotaxin-1/CC chemokine ligand 11 expression in human airway smooth muscle cells. role of MAPK (Erk1/2, JNK, and p38) pathways. J Immunol 2006; 177:4064-71.
64. Verhasselt V, Vosters O, Beuneu C, Nicaise C, Stordeur P, Goldman M. Induction of FOXP3-expressing regulatory CD4pos T cells by human mature autologous dendritic cells. Eur J Immunol 2004; 34:762-72.
65. Adorini L, Penna G, Giarratana N, Uskokovic M. Tolerogenic dendritic cells induced by vitamin D receptor ligands enhance regulatory T cells inhibiting allograft rejection and autoimmune diseases. J Cell Biochem 2003; 88:227-33.
66. Barrat FJ, Cua DJ, Boonstra A et al. In vitro generation of interleukin 10-producing regulatory CD4(+) T cells is induced by immunosuppressive drugs and inhibited by T helper type 1 (Th1)- and Th2-inducing cytokines. J Exp Med 2002; 195:603-16.
67. Gonzalez-Rey E, Chorny A, Fernandez-Martin A, Ganea D, Delgado M. Vasoactive intestinal peptide generates human tolerogenic dendritic cells that induce CD4 and CD8 regulatory T cells. Blood 2006; 107:3632-8.
68. Levings MK, Gregori S, Tresoldi E, Cazzaniga S, Bonini C, Roncarolo MG. Differentiation of Tr1 cells by immature dendritic cells requires IL-10 but not CD25+CD4+ Tr cells. Blood 2005; 105:1162-9.
69. Masli S, Turpie B, Streilein JW. Thrombospondin orchestrates the tolerance-promoting properties of TGFbeta-treated antigen-presenting cells. Int Immunol 2006; 18:689-99.
70. Gorczynski RM, Kai Y, Miyake K. MD1 expression regulates development of regulatory T cells. J Immunol 2006; 177:1078-84.
71. Caramalho I, Lopes-Carvalho T, Ostler D, Zelenay S, Haury M, Demengeot J. Regulatory T cells selectively express toll-like receptors and are activated by lipopolysaccharide. J Exp Med 2003; 197:403-11.
72. Sutmuller RP, Morgan ME, Netea MG, Grauer O, Adema GJ. Toll-like receptors on regulatory T cells: expanding immune regulation. Trends Immunol 2006; 27:387-93.
73. Marshall JS, McCurdy JD, Olynych T. Toll-like receptor-mediated activation of mast cells: implications for allergic disease? Int Arch Allergy Immunol 2003; 132:87-97.
74. Varadaradjalou S, Feger F, Thieblemont N et al. Toll-like receptor 2 (TLR2) and TLR4 differentially activate human mast cells. Eur J Immunol 2003; 33:899-906.
75. McCormack PL, Wagstaff AJ. Ultra-short-course seasonal allergy vaccine (Pollinex Quattro). Drugs 2006; 66:931-8.
76. Puggioni F, Durham SR, Francis JN. Monophosphoryl lipid A (MPL) promotes allergen-induced immune deviation in favour of Th1 responses. Allergy 2005; 60:678-84.
77. Cox LS, Linnemann DL, Nolte H, Weldon D, Finegold I, Nelson HS. Sublingual immunotherapy: a comprehensive review. J Allergy Clin Immunol 2006; 117:1021-35.
78. Chisholm D, Libet L, Hayashi T, Horner AA. Airway peptidoglycan and immunostimulatory DNA exposures have divergent effects on the development of airway allergen hypersensitivities. J Allergy Clin Immunol 2004; 113:448-54.
79. Redecke V, Hacker H, Datta SK et al. Cutting edge: activation of Toll-like receptor 2 induces a Th2 immune response and promotes experimental asthma. J Immunol 2004; 172:2739-43.
80. Dillon S, Agrawal A, Van Dyke T et al. A Toll-like receptor 2 ligand stimulates Th2 responses in vivo, via induction of extracellular signal-regulated kinase mitogen-activated protein kinase and c-Fos in dendritic cells. J Immunol 2004; 172:4733-43.
81. McCurdy JD, Olynych TJ, Maher LH, Marshall JS. Cutting edge: distinct Toll-like receptor 2 activators selectively induce different classes of mediator production from human mast cells. J Immunol 2003; 170:1625-9.
82. Akdis CA, Kussebi F, Pulendran B et al. Inhibition of T helper 2-type responses, IgE production and eosinophilia by synthetic lipopeptides. Eur J Immunol 2003; 33:2717-26.
83. Patel M, Xu D, Kewin P et al. TLR2 agonist ameliorates established allergic airway inflammation by promoting Th1 response and not via regulatory T cells. J Immunol 2005; 174:7558-63.
84. Revets H, Pynaert G, Grooten J, De Baetselier P. Lipoprotein I, a TLR2/4 ligand modulates Th2-driven allergic immune responses. J Immunol 2005; 174:1097-103.
85. Velasco G, Campo M, Manrique OJ et al. Toll-like receptor 4 or 2 agonists decrease allergic inflammation. Am J Respir Cell Mol Biol 2005; 32:218-24.
86. Re F, Strominger JL. Toll-like receptor 2 (TLR2) and TLR4 differentially activate human dendritic cells. J Biol Chem 2001; 276:37692-9.
87. Taylor RC, Richmond P, Upham JW. Toll-like receptor 2 ligands inhibit T (H) 2 responses to mite allergen. J Allergy Clin Immunol 2006; 117:1148-54.
88. Liu H, Komai-Koma M, Xu D, Liew FY. Toll-like receptor 2 signaling modulates the functions of CD4+ CD25+ regulatory T cells. Proc Natl Acad Sci USA 2006; 103:7048-53.
89. Sutmuller RP, den Brok MH, Kramer M et al. Toll-like receptor 2 controls expansion and function of regulatory T cells. J Clin Invest 2006; 116:485-94.
90. Zanin-Zhorov A, Cahalon L, Tal G, Margalit R, Lider O, Cohen IR. Heat shock protein 60 enhances CD4+ CD25+ regulatory T cell function via innate TLR2 signaling. JClin Invest 2006; 116:2022-32.
91. Dillon S, Agrawal S, Banerjee K et al. Yeast zymosan, a stimulus for TLR2 and dectin-1, induces regulatory antigen-presenting cells and immunological tolerance. J Clin Invest 2006; 116:916-28.
92. van der Kleij D, Latz E, Brouwers JF et al. A novel host-parasite lipid cross-talk. Schistosomal lyso-phosphatidylserine activates Toll-like receptor 2 and affects immune polarization. J Biol Chem 2002; 277:48122-9.
93. Lauener RP, Birchler T, Adamski J et al. Expression of CD14 and Toll-like receptor 2 in farmers' and non-farmers' children. Lancet 2002; 360:465-6.
94. van der Kleij D, van den Biggelaar AH, Kruize YC et al. Responses to Toll-like receptor ligands in children living in areas where schistosome infections are endemic. J Infect Dis 2004; 189:1044-51.
95. Krieg AM. Therapeutic potential of Toll-like receptor 9 activation. Nat Rev Drug Discov 2006; 5:471-84.
96. Klinman DM. Immunotherapeutic uses of CpG oligodeoxynucleotides. Nat Rev Immunol 2004; 4:249-58.
97. Racila DM, Kline JN. Perspectives in asthma: molecular use of microbial products in asthma prevention and treatment. J Allergy Clin Immunol 2005; 116:1202-5.
98. Kline JN, Waldschmidt TJ, Businga TR et al. Modulation of airway inflammation by CpG oligodeoxynucleotides in a murine model of asthma. J Immunol 1998; 160:2555-9.
99. Santeliz JV, Van Nest G, Traquina P, Larsen E, Wills-Karp M. Amb a 1-linked CpG oligodeoxynucleotides reverse established airway hyperresponsiveness in a murine model of asthma. J Allergy Clin Immunol 2002; 109:455-62.
100. Simons FE, Shikishima Y, Van Nest G, Eiden JJ, HayGlass KT. Selective immune redirection in humans with ragweed allergy by injecting Amb a 1 linked to immunostimulatory DNA. J Allergy Clin Immunol 2004; 113:1144-51.
101. Tulic MK, Fiset PO, Christodoulopoulos P et al. Amb a 1-immunostimulatory oligodeoxynucleotide conjugate immunotherapy decreases the nasal inflammatory response. J Allergy Clin Immunol 2004; 113:235-41.
102. Sur S, Wild JS, Choudhury BK, Sur N, Alam R, Klinman DM. Long term prevention of allergic lung inflammation in a mouse model of asthma by CpG oligodeoxynucleotides. J Immunol 1999; 162:6284-93.
103. Jain VV, Kitagaki K, Businga T et al. CpG-oligodeoxynucleotides inhibit airway remodeling in a murine model of chronic asthma. J Allergy Clin Immunol 2002; 110:867-72.
104. Fanucchi MV, Schelegle ES, Baker GL et al. Immunostimulatory oligonucleotides attenuate airways remodeling in allergic monkeys. Am J Respir Crit Care Med 2004; 170:1153-7.
105. Kline JN, Krieg AM, Waldschmidt TJ, Ballas ZK, Jain V, Businga TR. CpG oligodeoxynucleotides do not require TH1 cytokines to prevent eosinophilic airway inflammation in a murine model of asthma. J Allergy Clin Immunol 1999; 104:1258-64.
106. Horner AA, Widhopf GF, Burger JA et al. Immunostimulatory DNA inhibits IL-4-dependent IgE synthesis by human B cells. J Allergy Clin Immunol 2001; 108:417-23.
107. Lin L, Gerth AJ, Peng SL. CpG DNA redirects class-switching towards 'Th1-like' Ig isotype production via TLR9 and MyD88. Eur J Immunol 2004; 34:1483-7.
108. Hayashi T, Gong X, Rossetto C et al. Induction and inhibition of the Th2 phenotype spread: implications for childhood asthma. J Immunol 2005; 174:5864-73.
109. Hayashi T, Beck L, Rossetto C et al. Inhibition of experimental asthma by indoleamine 2,3-dioxygenase. J Clin Invest 2004; 114:270-9.
110. de Heer HJ, Hammad H, Soullie T et al. Essential role of lung plasmacytoid dendritic cells in preventing asthmatic reactions to harmless inhaled antigen. J Exp Med 2004; 200:89-98.
111. Hammad H, Lambrecht BN. Recent progress in the biology of airway dendritic cells and implications for understanding the regulation of asthmatic inflammation. J Allergy Clin Immunol 2006; 118:331-6.
112. Brugnolo F, Sampognaro S, Liotta F et al. The novel synthetic immune response modifier R-848 (Resiquimod) shifts human allergen-specific CD4+ TH2 lymphocytes into IFNgamma-producing cells. J Allergy Clin Immunol 2003; 111:380-8.
113. Fili L, Ferri S, Guarna F et al. Redirection of allergen-specific TH2 responses by a modified adenine through Toll-like receptor 7 interaction and IL-12/IFN release. J Allergy Clin Immunol 2006;118:511-7.
114. Johansen P, Senti G, Martinez Gomez JM et al. Toll-like receptor ligands as adjuvants in allergen-specific immunotherapy. Clin Exp Allergy 2005; 35:1591-8.
115. Frotscher B, Anton K, Worm M. Inhibition of IgE production by the imidazoquinoline resiquimod in nonallergic and allergic donors. J Invest Dermatol 2002; 119:1059-64.
116. Quarcoo D, Weixler S, Joachim RA et al. Resiquimod, a new immune response modifier from the family of imidazoquinolinamines, inhibits allergen-induced Th2 responses, airway inflammation and airway hyper-reactivity in mice. Clin Exp Allergy 2004; 34:1314-20.
117. Caron G, Duluc D, Fremaux I et al. Direct stimulation of human T cells via TLR5 and TLR7/8: flagellin and R-848 up-regulate proliferation and IFN-gamma production by memory CD4+ T cells. J Immunol 2005; 175:1551-7.
118. Segal BM, Chang JT, Shevach EM. CpG oligonucleotides are potent adjuvants for the activation of autoreactive encephalitogenic T cells in vivo. J Immunol 2000; 164:5683-8.
119. Langrish CL, Chen Y, Blumenschein WM et al. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med 2005; 201:233-40.