A toll-like receptor 2/6 agonist reduces allergic airway inflammation in chronic respiratory sensitisation to timothy grass pollen antigens

International Archives of Allergy and Immunology

Volumn 152, Issue 2, 2010, Pages 131-139

  Fuchs, Barbara ^a   Knothe, Saskia ^a   Rochlitzer, Sabine ^a   Nassimi, Matthias ^a   Greweling, Marina ^d   Lauenstein, Hans Dieter ^b   Nassenstein, Christina ^a,e   Müller, Meike ^a   Ebensen, Thomas ^d   Dittrich, Anna Maria ^c   Krug, Norbert ^a   Guzman, Carlos A ^d   Braun, Armin ^a  

^a FRAUNHOFER INSTITUTE FOR TOXICOLOGY AND EXPERIMENTAL MEDICINE   (Germany)

^b HANNOVER MEDICAL SCHOOL   (Germany)

^c Junior Research Group   (Germany)

^d HELMHOLTZ CENTRE FOR INFECTION RESEARCH   (Germany)

^e JOHNS HOPKINS ASTHMA AND ALLERGY CENTER   (United States)

Author keywords

Chronic allergic airway inflammation; Hygiene hypothesis; Rebalancing of T helper responses; Respiratory sensitisation; Timothy grass pollen allergens; Toll like receptor 2 6

Indexed keywords

BISACYCLOXYPROPYLCYSTEINE POLYETHYLENE GLYCOL CONJUGATE; CD4 ANTIGEN; CYTOKINE; DEXAMETHASONE; GAMMA INTERFERON; IMMUNOGLOBULIN G1; POLLEN ANTIGEN; TOLL LIKE RECEPTOR 2 AGONIST; TOLL LIKE RECEPTOR 6 AGONIST; TOLL LIKE RECEPTOR AGONIST; TRANSCRIPTION FACTOR FOXP3; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CELLULAR IMMUNITY; CONTROLLED STUDY; DRUG EFFECT; DRUG MECHANISM; EOSINOPHIL; FEMALE; FLOW CYTOMETRY; GRASS POLLEN; HISTOLOGY; IMMUNOGLOBULIN BLOOD LEVEL; IMMUNOMODULATION; IN VITRO STUDY; LUNG LAVAGE; LYMPH NODE; LYMPHOCYTE COUNT; MOUSE; NONHUMAN; PHLEUM PRATENSE; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; RESPIRATORY TRACT ALLERGY; RESPIRATORY TRACT INFLAMMATION; SENSITIZATION; SPLEEN CELL; TH1 CELL;

ANIMALS; ANTIGEN-PRESENTING CELLS; ANTIGENS, CD11C; ANTIGENS, CD45; ANTIGENS, PLANT; BRONCHOALVEOLAR LAVAGE FLUID; CELL COUNT; CHEMOKINES; CYTOKINES; DEXAMETHASONE; FEMALE; IMMUNIZATION; IMMUNOGLOBULIN G; INFLAMMATION; INTERFERON-GAMMA; INTERLEUKIN-5; LIPOPEPTIDES; LUNG; LYMPH NODES; MICE; MICE, INBRED BALB C; PHLEUM; POLLEN; POLYETHYLENE GLYCOLS; RESPIRATORY HYPERSENSITIVITY; SPLEEN; T-LYMPHOCYTES; T-LYMPHOCYTES, REGULATORY; TH1 CELLS; TOLL-LIKE RECEPTOR 2; TOLL-LIKE RECEPTOR 6;

EID: 72049121657     PISSN: 10182438     EISSN: None     Source Type: Journal    
DOI: 10.1159/000265534     Document Type: Article

References (35)

1. D'Amato G, Liccardi G, Frenguelli G: Thunderstorm-asthma and pollen allergy. Allergy 2007;62:11-16.
2. Traidl-Hoffmann C, Kasche A, Menzel A, Jakob T, Thiel M, Ring J, Behrendt H: Impact of pollen on human health: more than allergen carriers? Int Arch Allergy Immunol 2003;131:1-13.
3. Akdis C, Barlan I, Bahceciler N, Akdis M: Immunological mechanisms of sublingual immunotherapy. Allergy 2006;61(suppl 81):11-14.
4. Strachan D: Hay fever, hygiene and household size. Br Med J 1989;299:1259-1260.
5. Yazdanbakhsh M, Kremsner PG, van Ree R: Allergy, parasites, and the hygiene hypothesis. Science 2002;296:490-494.
6. Braun-Fahrlander C, Riedler J, Herz U, Eder W, Waser M, Grize L, Maisch S, Carr D, Gerlach F, Bufe A, Lauener RP, Schierl R, Renz H, Nowak D, von Mutius E; Allergy and Endotoxin Study Team: Environmental exposure to endotoxin and its relation to asthma in school-age children. N Engl J Med 2002;347:869-877.
7. Sukkar MB, Xie S, Khorasani NM, Kon OM, Stanbridge R, Issa R, Chung KF: Toll-like receptor 2, 3, and 4 expression and function in human airway smooth muscle. J Allergy Clin Immunol 2006;118:641-648.
8. Wilde I, Lotz S, Engelmann D, Starke A, van Zandberg G, Solbach W, Laskay T: Direct stimulatory effects of the TLR2/6 ligand bacterial lipopeptide MALP-2 on neutrophil granulocytes. Med Microbiol Immunol 2007;196:61-71.
9. Luhrmann A, Grote S, Stephan M, Tschernig T, Pabst R: Local pulmonary immune stimulation by the Toll-like receptor 2 and 6 ligand MALP-2 in rats is age dependent. Immunol Lett 2007;108:167-173.
10. Borsutzky S, Kretschmer K, Becker PD, Muhlradt PF, Kirschning CJ, Weiss S, Guzman CA: The mucosal adjuvant macrophage-activating lipopeptide-2 directly stimulates B lymphocytes via the TLR2 without the need of accessory cells. J Immunol 2005;174:6308-6313.
11. Medzhitov R, Preston-Hurlburt P, Janeway C Jr: A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 1997;388:394-397.
12. Blander JM, Medzhitov R: Toll-dependent selection of microbial antigens for presentation by dendritic cells. Nature 2006;440:808-812.
13. Raby BA, Klimecki WT, Laprise C, Renaud Y, Faith J, Lemire M, Greenwood C, Weiland K, Lange C, Palmer LJ, Lazarus R, Vercelli D, Kwiatkowski DJ, Silverman EK, Martinez FD, Hudson TJ, Weiss ST: Polymorphisms in toll-like receptor 4 are not associated with asthma or atopy-related phenotypes. Am J Respir Crit Care Med 2002;166:1449-1456.
14. Eder W, Klimecki W, Yu L, von Mutius E, Riedler J, Braun-Fahrlander C, Nowak D, Martinez FD, ALEX Study Team: Toll-like receptor 2 as a major gene for asthma in children of European farmers. J Allergy Clin Immunol 2004;113:482-488.
15. Takeuchi O, Kawai T, Muhlradt P, Morr M, Radolf JD, Zychlinsky A, Takeda K, Akira S: Discrimination of bacterial lipoproteins by Toll-like receptor 6. Int Immunol 2001;13:933-940.
16. Wu Q, Martin RJ, Rino JG, Jeyaseelan S, Breed R, Chu HW: A deficient TLR2 signaling promotes airway mucin production in Mycoplasma pneumoniae-infected allergic mice. Am J Physiol Lung Cell Mol Physiol 2007;292: L1064-L1072.
17. Hansbro P, Beagley K, Horvat J, Gibson P: Role of atypical bacterial infection of the lung in predisposition/protection of asthma. Pharmacol Ther 2004;101:193-210.
18. Muhlradt P, Kiess M, Meyer H, Sussmuth R, Jung G: Isolation, structure elucidation, and synthesis of macrophage stimulatory lipopeptide from Myco pla sma fe rment an s acting at picomolar concentrations. J Exp Med 1997;13:266-267.
19. Weigt H, Muhlradt P, Emmendorffer A, Krug N, Braun A: Synthetic mycoplasma-derived lipopeptide MALP-2 induces maturation and function of dendritic cells. Immunobiology 2003;207:223-233.
20. Weigt H, Nassenstein C, Tschernig T, Muhlradt PF, Krug N, Braun A: Efficacy of macrophage-activating lipopeptide-2 combined with interferon-gamma in a murine asthma model. Am J Respir Crit Care Med 2005;172:566-572.
21. Lührmann A, Tschernig T, Pabst R, Niewiesk S: Improved intranasal immunization with live-attenuated measles after co-inoculation of the lipopeptide MALP-2. Vaccine 2005;23:4721-4726.
22. Rharbaoui F, Drabner B, Borsutzky S, Winckler U, Morr M, Ensoli B, Mühlradt P, Guzman C: The Mycoplasma-derived lipopeptide MALP-2 is a potent mucosal adjuvant. Eur J Immunol 2002;32:2857-2865.
23. Link C, Gavioli R, Ebensen T, Canella A, Reinhard E, Guzman C: The Toll-like receptor ligand MALP-2 stimulates dendritic cell maturation and modulates proteasome composition and activity. Eur J Immunol 2004;34:899-907.
24. Rharbaoui F, Westendorf A, Link C, Felk S, Buer J, Gunzer M, Guzman C: The Mycoplasma-derived macrophage-activating 2-kilodalton lipopeptide triggers global immune activation on nasal mucosa-associated lymphoid tissues. Infect Immun 2004;72:6978-6986.
25. Deiters U, Barsig J, Tawil B, Muhlradt PF: The macrophage-activating lipopeptide-2 accelerates wound healing in diabetic mice. Exp Dermatol 2004;13:731-739.
26. Schmidt J, Welsch T, Jager D, Muhlradt P, Buchler M, Marten A: Intratumoural injection of the toll-like receptor-2/6 agonist 'macrophage-activating lipopeptide-2' in patients with pancreatic carcinoma: a phase I/II trial. Br J Cancer 2007;97:598-604.
27. Ellis R, Leigh R, Southam D, O'Byrne P, Inman M: Morphometric analysis of mouse airways after chronic allergen challenge. Lab Invest 2003;83:1285-1291.
28. Hirota J, Ellis R, Inman M: Regional differences in the pattern of airway remodelling following chronic allergen exposure in mice. Respir Res 2006;7:120.
29. Johnson J, Wiley R, Fattouh R, Swirski F, Gajewska B, Coyle A, Gutierrez-Ramos J, Ellis R, Inman M, Jordana M: Continuous exposure to house dust mite elicits chronic airway inflammation and structural remodeling. Am J Crit Care Med 2004;169:378-385. (Pubitemid 38134818)
30. Herz U, Renz H, Wiedermann U: Animal models of type I allergy using recombinant allergens. Methods 2004;32:271-280.
31. Vrtala S, Ball T, Spitzauer S, Pandjaitan B, Suphioglu C, Knox B, Sperr W, Valent P, Kraft D, Valenta R: Immunization with purified natural and recombinant allergens induces mouse IgG1 antibodies that recognize similar epitopes as human IgE and inhibit the human IgE-allergen interaction and allergen-induced basophil degranulation. J Immunol 1998;160:6137-6144.
32. neg bone marrow precursors in a mouse model of asthma. Blood 2002;100:3663-3671.
33. Moller G, Overbeek S, Van Helden-Meeuwsen C, Van Haarst J, Prens E, Mulder P, Postma D, Hoogsteden H: Increased numbers of dendritic cells in the bronchial mucosa of atopic asthmatic patients: downregulation by inhaled corticosteroids. Clin Exp Allergy 1996;26:517-524.
34. Patel M, Xu D, Kewin P, Choo-Kang B, McSharry C, Thomson NC, Liew F: TLR2 agonist ameliorates allergic airway inflammation by promoting Th1 response and not via regulatory T cells. J Immunol 2005;174:7558-7563.
35. Spiller S, Elson G, Ferstl R, Dreher S, Mueller T, Freudenberg M, Daubeuf B, Wagner H, Kirschning C: TLR4-induced IFN-gamma production increases TLR2 sensitivity and drives Gram-negative sepsis in mice. J Exp Med 2008;205:1747-1754.