Immunotherapy of experimental asthma by agonists of toll-like receptors, infection or tolerance

Abstract

Allergy prevalence and severity of asthma are increasing worldwide. Asthma is a chronic lung inflammatory syndrome and its classical phenotype is associated with deregulated activity of Thelper2 (Th2) cells. The current therapies to asthmatic patients are basically symptomatic and not therapeutic. Murine models have been developed to study asthma mechanisms and ovalbumin (OVA) is the most widely used allergen. However, OVA is considered a food- and not an airway born-allergen. Therefore, animal models of lung allergies have been adapted to airway born allergens, such as to those derived from mites present in household dust. We have recently developed an asthma model of allergic asthma using allergens from Blomia tropicalis (Bt), one of the most prevalent mite in tropical countries. Previous and recent work of our group using the OVA-model showed two potent immunotherapic mechanisms for the attenuation of allergic reactions: activation of the immune system by toll-like receptor (TLR) agonists or by mycobacteria infection and by the induction of specific- or cross-immunological tolerance. Based on these studies and in unpublished recent data we postulated that these immune mechanisms attenuate allergic responses by direct or indirect inhibition of Th2 cells' activities. I.e., our experiments with TLR agonists, infection with mycobacteria and tolerance indicate that experimental asthma could be controlled by inhibiting the development Th2 immunity or by suppressing its activities. The present project aims to outline prophylactic but mainly therapeutic applications of TLR agonists and/or mycobacteria conjunctly or not with cross-tolerance in regulating OVA or Bt-induced experimental asthma. (AU)