Contribution of Classic and Alternative Effector Pathways in Peanut-Induced Anaphylactic Responses

Abstract

Food allergy affects approximately 5% of children and is the leading cause of hospitalization for anaphylactic reactions in westernized countries. However, the pathways of anaphylaxis in food allergy are still relatively unknown. We investigated the effector pathways of allergic and anaphylactic responses of different strains of mice in a clinical relevant model of peanut allergy. C3H/HeOuJ, C57BL/6 and BALB/c mice were sensitized by intragastric peanut extract and challenged by intragastric or intraperitoneal injection of peanut. Peanut-specific T cell responses, IgE, IgG1 and IgG2a and mucosal mast cell degranulation were induced to different extent in C3H/HeOuJ, C57BL/6 and BALB/c mice. Interestingly, anaphylactic symptoms after systemic challenge were highest in C3H/HeOuJ followed by C57BL/6 but were absent in BALB/c mice. Mechanistic studies showed that the food allergic systemic anaphylaxis was dependent on platelets, FcRγ and mast cells, and partially dependent on platelet activating factor and monocytes/macrophages, depending on mouse strain. These data demonstrate that in three mouse strains, components of the classic and alternative anaphylactic cascade are differently expressed, leading to differential outcomes in parameters of allergic disease and food induced systemic anaphylaxis.

Differences in the Anaphylactic Response between C3H/HeOuJ and BALB/c Mice

“…Interestingly, no antigen-specific IgE was observed in C3H/HeSn, thus contrasting with our results. Nevertheless, an oral peanut sensitization study showed heterogeneous outcomes in the anaphylactic responses in C3H/HeOuJ mice [24] and C3H/HeJ mice [20] compared with BALB/c mice. In both cases, C3H/HeOuJ and C3H/HeJ always had a higher clinical score upon challenge than the BALB/c group, as demonstrated in our data.…”

“…In both cases, C3H/HeOuJ and C3H/HeJ always had a higher clinical score upon challenge than the BALB/c group, as demonstrated in our data. However, in their model, C3H/HeOuJ mice were shown to generate increased amounts of antigen-specific IgA and IgG2a, while C3H/HeJ mice [20] and BALB/c mice [24] showed an increase in antigen-specific IgE levels. Another difference with our model is the cytokine release pattern.…”

“…Thus, allergic sensitization was strain dependent in their model. In addition, Morafo et al [20] and Smit et al [24] contrasted susceptibility to induction of food allergy, respectively, in C3H/HeJ and BALB/c and C3H/HeOuJ, BALB/cByJ, and C57BL/6J mice. These authors showed that C3H/HeJ and C3H/HeOuJ mice had more severe anaphylactic symptoms than BALB/c and BALB/cByJ mice.…”

Dietary Elimination of Soybean Components Enhances Allergic Immune Response to Peanuts in BALB/c Mice

“…Most mouse strains require an adjuvant to break mucosal tolerance and to mount an immune response to oral/intragastric sensitization with food allergens, with BALB/c mice being among the best responders in terms of IgE response. Yet, BALB/c mice do not show detectable anaphylaxis following oral challenge with the allergen and a minimal response when challenged via the intraperitoneal route [8,9]. Allergen-specific IgE levels in C3H/HeJ and C3H/HeOuJ mice are significantly lower compared to BALB/c, but these mice readily develop anaphylaxis upon challenge, closely mimicking human food allergy [8,10,11].…”

“…Yet, BALB/c mice do not show detectable anaphylaxis following oral challenge with the allergen and a minimal response when challenged via the intraperitoneal route [8,9]. Allergen-specific IgE levels in C3H/HeJ and C3H/HeOuJ mice are significantly lower compared to BALB/c, but these mice readily develop anaphylaxis upon challenge, closely mimicking human food allergy [8,10,11]. A number of studies in these mouse models have contributed towards developing new therapies for peanut allergy [12].…”