A Toll-Like Receptor 2/6 Agonist Reduces Allergic Airway Inflammation in Chronic Respiratory Sensitisation to Timothy Grass Pollen Antigens

作者：Fuchs Barbara; Knothe Saskia; Rochlitzer Sabine; Nassimi Matthias; Greweling Marina; Lauenstein Hans Dieter; Nassenstein Christina; Mueller Meike; Ebensen Thomas; Dittrich Anna Maria; Krug Norbert; Guzman Carlos A; Braun Armin^*

来源：International Archives of Allergy and Immunology, 2010, 152(2): 131-139.

DOI：10.1159/000265534

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

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.

• 出版日期2010