Immunotherapy of experimental asthma by agonists of toll-like receptors

Abstract

The prevalence and severity of allergy, including asthma, are on the rise worldwide. At present, asthma is considered a lung chronic inflammatory disease and its classic form is associated with uncontrolled T helper (Th)2 cells activity. Murine models have been developed to investigate mechanisms of asthma, and ovalbumin (OVA) is the most commonly used allergen. However, this protein is a food and not an airborne allergen. Experimental models of lung allergic disease were then adapted to airborne allergens such as those derived from house dust mite. Blomia tropicalis (Bt) is the most prevalent mite in Brazil. In our lab, we recently developed an experimental model of allergic asthma using Bt extract. In previous studies using OVA as allergen, we have shown that immune activation by agonists of Toll-like receptors (TLR)s is a potent mechanism to attenuate allergic reactions. Based on these studies and on recent data, we postulated that TLR agonists can attenuate allergic responses by direct or indirect inhibition of Th2 activity. The present project aims to delineate prophylactic but mainly therapeutic applications of TLR agonists to inhibit asthma using OVA or Bt extract as allergens.