• Barbara Fuchs, Saskia Knothe, Sabine Rochlitzer, Matthias Nassimi, Marina Greweling, Hans-Dieter Lauenstein, Christina Nassenstein, Meike Müller, Thomas Ebensen, Anna-Maria Dittrich, Norbert Krug, Carlos A Guzman, and Armin Braun.
• Department of Immunology, Allergology and Immunotoxicology, Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany.
• Int. Arch. Allergy Immunol. 2010 Jan 1; 152 (2): 131-9.

BackgroundThe 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.MethodsIn 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.ResultsEosinophilic 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.ConclusionThe 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.Copyright 2009 S. Karger AG, Basel.

82 keywords...

hide…