Inhibition of glycolysis alleviates food allergy via regulating the immune response of T helper cells and mast cells to ovalbumin in sensitized mice

Abstract

Ingestion of food allergens can elicit metabolic alterations in the host during the induction of allergic responses. Gaining a grasp of the key events underlying these changes will contribute to a better understanding of the mechanism of food allergy. In this study, we aimed to investigate the role of glycolysis, an important metabolic pathway, in the development of food allergy (FA). The glycolysis inhibitor 2-deoxy-D-glucose (2-DG) was utilized in an ovalbumin (OVA)-induced FA mouse model prior to oral allergen challenges, and the results found that inhibition of glycolysis effectively alleviated allergic diarrhea (2-DG group: 0% vs. FA group: 100%) and significantly decreased allergen-specific IgE levels. Further analysis revealed the inhibiting effect of 2-DG intervention on the systemic and intestinal Th2 immune responses, mainly manifested by suppressed Th2 cell differentiation and IL-4 expression. Additionally, blockade of glycolysis was shown to decrease intestinal mast cell accumulation, serum mast cell protease-1 levels, and the expression of typical mast cell markers (e.g., Fcer1a, Mcpt1, and Il1rl1). Moreover, in vitro experiments indicated that blockade of glycolysis by 2-DG dampened early receptor signaling in mast cell activation and its function. In summary, these results demonstrate that the glycolytic metabolic pathway was deeply involved in FA, and that the alleviation of allergic reactions by glycolysis inhibition was achieved via modulating the synergistic immune response of Th2 cells and mast cells to ingested allergens.