Journal Article
. 2008 Nov; 123(1):231-238.e4.
doi: 10.1016/j.jaci.2008.10.011.

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

Kirthana Ganeshan 1 Colleen V Neilsen  April Hadsaitong  Robert P Schleimer  Xunrong Luo  Paul J Bryce  
  • PMID: 19022495
  •     60 References
  •     61 citations


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 T(H)2 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-beta 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.

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Allergy, 2019 Jun 13; 75(2). PMID: 31187876    Free PMC article.
Cutaneous Exposure to Clinically Relevant Lone Star Ticks Promotes IgE Production and Hypersensitivity through CD4+ T Cell- and MyD88-Dependent Pathways in Mice.
Jessica L Chandrasekhar, Kelly M Cox, +3 authors, Loren D Erickson.
J Immunol, 2019 Jul 05; 203(4). PMID: 31270149    Free PMC article.
Host-microbial interactions in patients with chronic rhinosinusitis.
Daniel L Hamilos.
J Allergy Clin Immunol, 2013 Dec 03; 133(3). PMID: 24290275    Free PMC article.
Genetic diversity between mouse strains allows identification of the CC027/GeniUnc strain as an orally reactive model of peanut allergy.
Kelly Orgel, Johanna M Smeekens, +7 authors, Michael D Kulis.
J Allergy Clin Immunol, 2018 Oct 22; 143(3). PMID: 30342892    Free PMC article.
Group 2 Innate Lymphoid Cells Promote Development of T Follicular Helper Cells and Initiate Allergic Sensitization to Peanuts.
James W Krempski, Takao Kobayashi, +2 authors, Hirohito Kita.
J Immunol, 2020 May 06; 204(12). PMID: 32366582    Free PMC article.
Epicutaneous sensitization in the development of food allergy: What is the evidence and how can this be prevented?
Helen A Brough, Kari C Nadeau, +5 authors, Gideon Lack.
Allergy, 2020 Apr 07; 75(9). PMID: 32249942    Free PMC article.
Immunological Outcomes of Allergen-Specific Immunotherapy in Food Allergy.
Ann-Marie Malby Schoos, Dominique Bullens, +20 authors, Willem van de Veen.
Front Immunol, 2020 Nov 24; 11. PMID: 33224138    Free PMC article.
Advances in Molecular Mechanisms of Wheat Allergenicity in Animal Models: A Comprehensive Review.
Yining Jin, Harini G Acharya, +5 authors, Venugopal Gangur.
Molecules, 2019 Mar 27; 24(6). PMID: 30909404    Free PMC article.
Perturbations to Homeostasis in Experimental Models Revealed Innate Pathways Driving Food Allergy.
Kelly Bruton, Joshua F E Koenig, Allyssa Phelps, Manel Jordana.
Front Immunol, 2020 Dec 29; 11. PMID: 33362786    Free PMC article.
Antigen-Presenting Cells in Food Tolerance and Allergy.
Elise G Liu, Xiangyun Yin, Anush Swaminathan, Stephanie C Eisenbarth.
Front Immunol, 2021 Jan 26; 11. PMID: 33488627    Free PMC article.