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

 
: Fuchs, B.; Knothe, S.; Rochlitzer, S.; Nassimi, M.; Greweling, M.; Lauenstein, H.D.; Nassenstein, C.; Müller, M.; Ebensen, T.; Dittrich, A.M.; Krug, N.; Guzman, C.A.; Braun, A.

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International archives of allergy and immunology 152 (2010), No.2, pp.131-139
ISSN: 1018-2438
English
Journal Article
Fraunhofer ITEM ()
toll-like receptor 2/6; hygiene hypothesis; chronic allergic airway inflammation; respiratory sensitisation; rebalancing of T helper responses; Timothy grass pollen allergens

Abstract
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)-gamma 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-gamma. 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.

: http://publica.fraunhofer.de/documents/N-125043.html