Genetic susceptibility to food allergy is linked to differential TH2-TH1 responses in C3H/HeJ and BALB/c mice

Abstract

Background: Although food allergy is a serious health problem in westernized countries, factors influencing the development of food allergy are largely unknown. Appropriate murine models of food allergy would be useful in understanding the mechanisms underlying food allergy in human subjects. Objective: We sought to determine the susceptibility of different strains of mice to food hypersensitivity. Methods: C3H/HeJ and BALB/c mice were sensitized to cow's milk (CM) or peanut by means of intragastric administration, with cholera toxin as a mucosal adjuvant. Mice were then challenged with CM or peanut. Antigen-specific IgE levels, anaphylactic symptoms, plasma histamine levels, and splenocyte cytokine profiles of these 2 strains were compared. Results: CM-specific IgE levels were significantly increased only in the C3H/HeJ strain, 87% of which exhibited systemic anaphylactic reactions accompanied by significantly increased plasma histamine levels in response to challenge. BALB/c mice exhibited no significant CM-specific IgE response, increased plasma histamine levels, or anaphylactic symptoms. After peanut challenge, 100% of peanut-sensitized C3H/HeJ mice exhibited high levels of peanut-specific IgE and anaphylactic symptoms. In contrast, no hypersensitivity reactions were detected in BALB/c mice, despite the presence of significant serum peanut-specific IgE levels. Splenocytes from CM- and peanut-sensitized C3H/HeJ mice exhibited significantly increased IL-4 and IL-10 secretion, whereas splenocytes from BALB/c mice exhibited significantly increased IFN-γ secretion. Conclusion: Induction of food-induced hypersensitivity reactions in mice is strain dependent, with C3H/HeJ mice being susceptible and BALB/c mice being resistant. This strain-dependent susceptibility to food allergy is associated with differential TH2-TH1 responses after intragastric food allergen sensitization.