A Toll-Like Receptor 2/6 Agonist Reduces Allergic Airway Inflammation in Chronic Respiratory Sensitisation to Timothy Grass Pollen Antigens
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Barbara Fuchs a, d Saskia Knothe a Sabine Rochlitzer a Matthias Nassimi a Marina Greweling e Hans-Dieter Lauenstein b Christina Nassenstein a, f Mei
- چاپ و سال / کشور: 2009
Description
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 dexamethasonewith 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+ antigenpresenting 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.
Int Arch Allergy Immunol 2010;152:131–139 Received: November 3, 2008 Accepted after revision: August 4, 2009 Published online: December 16, 2009
