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 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.
Ganeshan
Kirthana
K
Division of Allergy-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60610, USA.
Neilsen
Colleen V
CV
Hadsaitong
April
A
Schleimer
Robert P
RP
Luo
Xunrong
X
Bryce
Paul J
PJ
D000485:Allergens / Q000276:immunology*; D000707:Anaphylaxis / Q000139:chemically induced / Q000276:immunology*; D000818:Animals; D010367:Arachis / Q000276:immunology; D015550:Cell Degranulation / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D004768:Enterotoxins / Q000633:toxicity*; D004802:Eosinophilia / Q000139:chemically induced / Q000276:immunology; D005260:Female; D005512:Food Hypersensitivity / Q000209:etiology / Q000276:immunology*; D007108:Immune Tolerance / Q000187:drug effects*; D008407:Mast Cells / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000276:immunology
D000485:Allergens; D004768:Enterotoxins; D016212:Transforming Growth Factor beta; C031818:enterotoxin B, staphylococcal