Modelo de Alergia a Ovalbumina em Animais Não Obesos Diabéticos (NOD)

Abstract

Type 1 diabetes mellitus is a chronic autoimmune disease characterized by the selective destruction of pancreatic beta cells located in the islets of Langerhans and responsible for insulin production. This process, mediated primarily by autoreactive T lymphocytes, results in absolute insulin deficiency, a hormone essential for glucose uptake by tissues. The development of the disease involves the interaction of genetic and environmental factors, alterations in the intestinal microbiota, and dietary components, which contribute to the breakdown of immunological tolerance. In addition to metabolic alterations, type 1 diabetes is associated with acute and chronic complications and is considered a major public health problem. Recent studies show that NOD mice that spontaneously develop type 1 diabetes exhibit several alterations in the intestinal mucosa, including interfering with the establishment of oral tolerance. The intestinal mucosa is the largest surface in contact with the external environment, coming into continuous contact with dietary antigens and the commensal microbiota. Oral tolerance mechanisms are responsible for maintaining intestinal mucosal homeostasis and preventing inflammatory immune responses to dietary and microbiota antigens. It is known that a breakdown in oral tolerance can result in the development of food allergies. In this scenario, the hypothesis of this study is that alterations in the intestinal mucosa of NOD mice could interfere with the induction of food allergies in these animals. We evaluated the induction of food allergies in NOD mice by comparing them to BALB/c mice. Interestingly, although NOD mice exhibit defects in the intestinal mucosa and in the induction of oral tolerance, and contrary to what is described in the literature regarding allergic sensitization with low doses of allergens, the dose of the allergen ovalbumin (OVA) required to induce specific IgE production in these animals must be higher (100 μg) than that used (10 μg) to induce the same disease in BALB/c mice. Sensitization of NOD mice with 100 μg of OVA, but not with 1 or 10 μg of OVA adsorbed to AL(OH)3, led to increased serum IgE levels after oral challenge. The active cutaneous anaphylaxis test also showed that the high dose was most effective for mast cell degranulation, leading to increased vascular permeability. In histopathological analysis of the intestine, we showed that this dose induced an increase in the frequency of intraepithelial lymphocytes and the number of eosinophils in the lamina propria, characterizing an allergic inflammatory profile. Furthermore, the high dose accelerated the insulitis process, intensifying disease progression. The findings of this study reinforce the importance of the NOD model as an experimental tool for understanding possible mechanisms that may link autoimmune predisposition to the development of food allergic responses and how these responses occur.