Impairing oral tolerance promotes allergy and anaphylaxis: A new murine food allergy model

Background

Food allergy is a disorder in which antigenic food proteins elicit immune responses. Animal models of food allergy have several limitations that influence their utility, including failure to recapitulate several key immunologic hallmarks. Consequently, little is known regarding the pathogenesis and mechanisms leading to food allergy. Staphylococcus aureus–derived enterotoxins, a common cause of food contamination, are associated with antigen responses in atopic dermatitis.

Objective

We hypothesized that S aureus–derived enterotoxins might influence the development of food allergy. We examined the influence of administration of staphylococcal enterotoxin B (SEB) with food allergens on immunologic responses and compared these responses with those elicited by a cholera toxin–driven food allergy model.

Methods

Oral administration of ovalbumin or whole peanut extract with or without SEB was performed once weekly. After 8 weeks, mice were challenged with oral antigen alone, and the physiologic and immunologic responses to antigen were studied.

Results

SEB administered with antigen resulted in immune responses to the antigen. Responses were highly TH2 polarized, and oral challenge with antigen triggered anaphylaxis and local and systemic mast cell degranulation. SEB-driven sensitization induced eosinophilia in the blood and intestinal tissues not observed with cholera toxin sensitization. SEB impaired tolerance specifically by impairing expression of TGF-β and regulatory T cells, and tolerance was restored with high-dose antigen.

Conclusions

We demonstrate a new model of food allergy to oral antigen in common laboratory strains of mice that recapitulates many features of clinical food allergy that are not seen in other models. We demonstrate that SEB impairs oral tolerance and permits allergic responses.

Key words: Food allergy, Staphylococcus aureus enterotoxin B, TH2, anaphylaxis, murine, peanut, ovalbumin, tolerance, mast cells, eosinophils

Abbreviations used: AD, Atopic dermatitis, CT, Cholera toxin, OVA, Ovalbumin, SEB, Staphylococcal enterotoxin B, TIM, T-cell immunoglobulin and mucin domain molecule, Treg, Regulatory T, WPE, Whole peanut extract