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

Kirthana Ganeshan, Colleen V. Neilsen, April Hadsaitong, Robert P. Schleimer, Xunrong Luo, Paul J. Bryce*

*Corresponding author for this work

Research output: Contribution to journalArticle

120 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)231-238.e4
JournalJournal of Allergy and Clinical Immunology
Volume123
Issue number1
DOIs
StatePublished - Jan 2009

Keywords

  • Food allergy, Staphylococcus aureus enterotoxin B
  • T2
  • anaphylaxis
  • eosinophils
  • mast cells
  • murine
  • ovalbumin
  • peanut
  • tolerance

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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