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

Joost J Smit,Louis Van Bloois,Dietmar Zaiss,Maarten Pennings,Gert Storm,Danielle Fiechter,Ine Hassing,Raymond H H Pieters,Karina Willemsen,Jeanette H W Leusen,Jacques Zimmer

doi:10.1371/journal.pone.0028917

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.

Highlights

Food allergy is generally defined as an adverse health effect arising from a specific immune response that occurs reproducibly on exposure to a given food
Two pathways of systemic anaphylaxis have been demonstrated in mice: a classical pathway involving IgE, FceRI, mast cells and histamine versus an alternative pathway mediated by IgG, FccRIII, neutrophils, macrophages, basophils and platelet activating factor (PAF) [6,7]
We compared antibody responses in C3H/HeOuJ, C57BL/6 and BALB/c mice intragastrically exposed to peanut extract (PE) with cholera toxin (CT)

Summary

Introduction

Food allergy is generally defined as an adverse health effect arising from a specific immune response that occurs reproducibly on exposure to a given food. Despite that diagnosis of food allergy relies strongly on the detection of specific IgE and mast cell-mediated skin-prick testing, it is argued that allergic reactions may occur independently of antigen-specific IgE and mast cells [4].Already in the 70’s it was demonstrated that human anaphylaxis could be mediated by IgG antibodies [5]. Two pathways of systemic anaphylaxis have been demonstrated in mice: a classical pathway involving IgE, FceRI, mast cells and histamine versus an alternative pathway mediated by IgG, FccRIII, neutrophils, macrophages, basophils and platelet activating factor (PAF) [6,7]. Most mouse studies looking at the role of the alternative pathway of anaphylaxis did not use relevant food allergens, or used mice preconditioned for responsiveness by using vasoactive mediators [10,11,12]. Until now no evidence exists for a role of alternative pathway in food allergy and food-induced anaphylactic responses

Methods

Results

Conclusion