Immune response modulation to the antigenic components of the Polybia paulista venom(Hymenoptera, Vepidae) in a murine experimental model of allergy: effects of bystander suppression induced by oral tolerance to protein antigen.

Abstract

Insect sting allergy accounts for 14% of severe cases of allergic reactions in Latin America, resulting in a considerable morbidity and significant expenses for the treatment of the patients. Allergen-specific immunotherapy (AIT) is the only treatment with long-term effects, indicated for serious cases with risk of death due to anaphylaxis. However, AIT is ineffective in the treatment of multi-sensitized patients and could trigger intense adverse reactions for some types of allergens, mainly during the induction period and preliminary phases of maintenance of immunotherapy. To overcome these difficulties, the use of oral tolerance induction protocols with uncorrelated protein antigens can be a useful strategy. In this context, these antigens may induce mechanisms of peripheral tolerance, capable of suppressing the immune responses directed also to other antigens present nearby, a phenomenon known as bystander suppression. The present work aims to evaluate the immunomodulatory mechanisms, related to the bystander suppression in experimental mouse model of allergy to Polybia paulista (P. paulista) wasp venom. To this, oral tolerance induction protocols with the ovalbumin protein antigen (OVA) will be tested in BALB/c mice, which will be previously sensitized with P. paulista wasp venom antigens, and in mice that will be sensitized immediately after oral tolerance induction. In these experimental models, the humoral and cellular immune responses specific to OVA and to P. paulista venom protein antigens will be evaluated. For this purpose, the profile of antigen-specific immunoglobulins (sIgE, sIgG1 and sIgG2a) and the quantification of the protease derived from the activation of MCP-1 mast cells will be evaluated in serum samples. The functional profile of CD4+ T cells (Th1, Th2, Th9, Th17 and Tregs) and CD19+ IL-10+ regulatory B cell will be evaluated after in vitro stimulation of splenic lymphocytes. Additionally, we will analyze the involvement of tolerogenic dendritic cells (Tol-DCs) in this phenomenon, evaluating the expression of the costimulatory molecules and the enzymes IDO and ALDH, related with the suppressive activity exerted by these cells, as well as the effect of the adoptive transference of Tol-DCs in the mouse from the experimental groups described above. In this sense, the investigation of the immunomodulatory mechanisms, involved in the phenomena of bystander suppression, may contribute to future therapeutic interventions for the treatment of allergy to Hymenoptera's venom, with alternative protocols of AIT based on the use of uncorrelated protein antigens. (AU)