Oral Superantigen Promotes Th2-skewed Immune Responses and Anaphylaxis to Food Antigens

Abstract

RationaleFood allergy is characterized by the generation of immune responses to antigenic proteins in foods. Oral tolerance usually prevents such responses and the factors that promote food allergen sensitization in food allergy remain unknown. Enterotoxin-secreting strains of Staphylococcus aureus are associated with allergic diseases such as atopic dermatitis and chronic rhinosinusitis but are also a common cause of food contamination. We examined the influence of oral administration of Staphylococcal enterotoxin B (SEB) on the generation of oral tolerance to food allergens.MethodsBalb/c mice received OVA or whole peanut extract (WPE) by oral gavage once weekly for 8 weeks with or without addition of SEB. As a positive control, separate groups received antigen plus cholera toxin, a commonly utilized mucosal adjuvant. On week 9, mice were challenged with a single bolus administration of antigen and anaphylactic responses monitored. 24 hours later, samples were collected for immunological analysis.ResultsSEB promoted the generation of ovalbumin or peanut-specific IgE and anaphylaxis upon food antigen challenge. Challenge with BSA failed to elicit anaphylaxis. Unlike CT-driven sensitization, SEB promoted minimal antigen-specific IgG2a responses. Additionally, peripheral blood eosinophilia was significantly increased by SEB and not by CT-driven sensitization. CD3/CD28 and antigen stimulated splenocytes from SEB/Ag treated mice elicited a strong Th2-biased immune response while gene expression of Th2 cytokines in jejunum and mesenteric lymph nodes were also elevated.ConclusionsOur findings establish that oral exposure to SEB is sufficient to promote allergic responses and anaphylaxis to food antigens and demonstrates a promising new model for food allergy research. RationaleFood allergy is characterized by the generation of immune responses to antigenic proteins in foods. Oral tolerance usually prevents such responses and the factors that promote food allergen sensitization in food allergy remain unknown. Enterotoxin-secreting strains of Staphylococcus aureus are associated with allergic diseases such as atopic dermatitis and chronic rhinosinusitis but are also a common cause of food contamination. We examined the influence of oral administration of Staphylococcal enterotoxin B (SEB) on the generation of oral tolerance to food allergens. Food allergy is characterized by the generation of immune responses to antigenic proteins in foods. Oral tolerance usually prevents such responses and the factors that promote food allergen sensitization in food allergy remain unknown. Enterotoxin-secreting strains of Staphylococcus aureus are associated with allergic diseases such as atopic dermatitis and chronic rhinosinusitis but are also a common cause of food contamination. We examined the influence of oral administration of Staphylococcal enterotoxin B (SEB) on the generation of oral tolerance to food allergens. MethodsBalb/c mice received OVA or whole peanut extract (WPE) by oral gavage once weekly for 8 weeks with or without addition of SEB. As a positive control, separate groups received antigen plus cholera toxin, a commonly utilized mucosal adjuvant. On week 9, mice were challenged with a single bolus administration of antigen and anaphylactic responses monitored. 24 hours later, samples were collected for immunological analysis. Balb/c mice received OVA or whole peanut extract (WPE) by oral gavage once weekly for 8 weeks with or without addition of SEB. As a positive control, separate groups received antigen plus cholera toxin, a commonly utilized mucosal adjuvant. On week 9, mice were challenged with a single bolus administration of antigen and anaphylactic responses monitored. 24 hours later, samples were collected for immunological analysis. ResultsSEB promoted the generation of ovalbumin or peanut-specific IgE and anaphylaxis upon food antigen challenge. Challenge with BSA failed to elicit anaphylaxis. Unlike CT-driven sensitization, SEB promoted minimal antigen-specific IgG2a responses. Additionally, peripheral blood eosinophilia was significantly increased by SEB and not by CT-driven sensitization. CD3/CD28 and antigen stimulated splenocytes from SEB/Ag treated mice elicited a strong Th2-biased immune response while gene expression of Th2 cytokines in jejunum and mesenteric lymph nodes were also elevated. SEB promoted the generation of ovalbumin or peanut-specific IgE and anaphylaxis upon food antigen challenge. Challenge with BSA failed to elicit anaphylaxis. Unlike CT-driven sensitization, SEB promoted minimal antigen-specific IgG2a responses. Additionally, peripheral blood eosinophilia was significantly increased by SEB and not by CT-driven sensitization. CD3/CD28 and antigen stimulated splenocytes from SEB/Ag treated mice elicited a strong Th2-biased immune response while gene expression of Th2 cytokines in jejunum and mesenteric lymph nodes were also elevated. ConclusionsOur findings establish that oral exposure to SEB is sufficient to promote allergic responses and anaphylaxis to food antigens and demonstrates a promising new model for food allergy research. Our findings establish that oral exposure to SEB is sufficient to promote allergic responses and anaphylaxis to food antigens and demonstrates a promising new model for food allergy research.