A Toll-Like Receptor 2/6 Agonist Reduces Allergic Airway Inflammation in Chronic Respiratory Sensitisation to Timothy Grass Pollen Antigens
| Autor: | S. Knothe, Marina Greweling, Hans-Dieter Lauenstein, Christina Nassenstein, Matthias Nassimi, Meike Müller, Anna-Maria Dittrich, Sabine Rochlitzer, Barbara Fuchs, Norbert Krug, Armin Braun, Thomas Ebensen, Carlos A. Guzmán |
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| Přispěvatelé: | Publica |
| Rok vydání: | 2009 |
| Předmět: |
Allergy
T-Lymphocytes medicine.medical_treatment Cell Count T-Lymphocytes Regulatory hygiene hypothesis Dexamethasone Polyethylene Glycols Mice Immunology and Allergy Lung Mice Inbred BALB C chronic allergic airway inflammation Timothy grass pollen allergens FOXP3 General Medicine Cytokine medicine.anatomical_structure Cytokines Pollen Female Chemokines medicine.symptom Bronchoalveolar Lavage Fluid respiratory sensitisation Agonist medicine.drug_class T cell Immunology Antigen-Presenting Cells Inflammation Biology Allergic inflammation Interferon-gamma Lipopeptides Immune system Respiratory Hypersensitivity medicine Animals rebalancing of T helper responses toll-like receptor 2/6 Antigens Plant Th1 Cells medicine.disease Toll-Like Receptor 2 CD11c Antigen Toll-Like Receptor 6 Immunoglobulin G Phleum Leukocyte Common Antigens Immunization Lymph Nodes Interleukin-5 Spleen |
| Zdroj: | International Archives of Allergy and Immunology. 152:131-139 |
| ISSN: | 1423-0097 1018-2438 |
| Popis: | Background: The hygiene hypothesis negatively correlates the microbial burden of the environment with the prevalence of T helper type 2 (Th2)-related disorders, e.g. allergy and asthma. This is explained by Th1 triggering through pathogen-associated molecular patterns via Toll-like receptors (TLRs). In this study, the biological effects of a TLR2/6 agonist as a potential treatment of allergic inflammation are explored. Methods: In a model of chronic allergic airway inflammation induced by intranasal administration of Timothy grass pollen allergen extract, early TLR agonism and/or interferon (IFN)-γ administration was compared to the therapeutic and immune-modulating effects of dexamethasone with regard to the cellular inflammation and cytokine profiles. Results: Eosinophilic inflammation was clearly reduced by TLR2/6 agonism. This effect was also seen without simultaneous administration of IFN-γ. However, lymphocyte counts were not affected among the different treatment groups. More precise determination of the lymphocyte-mediated immune reaction showed that TLR2/6 agonism induced neither CD4+foxp3+ regulatory T cells in draining lymph nodes nor a pronounced Th1 immune response. In contrast, dexamethasone reduced both sensitisation as well as allergic inflammation and, in addition, CD11c+ antigen-presenting cells in lymph nodes. Our data clearly point to the potential to rebalance Th2-skewed allergic immune responses by therapeutic TLR2/6 agonist administration. Conclusion: The use of the TLR2/6 agonist is a promising therapeutic approach in diseases with an imbalance in T cell responses, such as allergy and asthma. |
| Databáze: | OpenAIRE |
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