Distinct immune effector pathways contribute to the full expression of peanut-induced anaphylactic reactions in mice

• Published in: Journal of allergy and clinical immunology 2011-06, Vol.127 (6), p.1552-1561.e1
• Main Authors: Arias, Katherine, BHSc, Chu, Derek K., BHSc, Flader, Kristin, BSc, Botelho, Fernando, PhD, Walker, Tina, BSc, Arias, Natalia, Humbles, Alison A., PhD, Coyle, Anthony J., PhD, Oettgen, Hans C., MD, PhD, Chang, Hyun-Dong, PhD, Van Rooijen, Nico, PhD, Waserman, Susan, MD, MSc, Jordana, Manel, MD, PhD
• Format: Article
• Language: English
• Subjects: Allergic diseases; Allergies; Allergy and Immunology; anaphylaxis; Anaphylaxis - etiology; Anaphylaxis - immunology; Anaphylaxis - prevention & control; Animals; Arachis hypogaea; basophils; Basophils - immunology; Biological and medical sciences; Digestive allergic diseases; Fatalities; FcγRIII; FcεRI; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; IgE; IgG1; Immunoglobulin E - metabolism; Immunoglobulin G - metabolism; Immunopathology; Kit W-sh/ W-sh; Laboratories; macrophages; Macrophages - immunology; mast cells; Mast Cells - immunology; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Mice, Mutant Strains; Peanut allergy; Peanut Hypersensitivity - etiology; Peanut Hypersensitivity - immunology; Receptors, IgG - metabolism; Rodents; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Signal Transduction - immunology
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2011.03.044

Background Food-induced anaphylaxis is often a severe allergic reaction characterized by multiorgan dysfunction and a potentially fatal outcome. Objectives We sought to investigate the relative contribution of immunoglobulin-dependent effector pathways to anaphylactic responses to food (ie, peanut). Methods Wild-type and various mutant mice were sensitized with peanut protein and cholera toxin by means of oral gavage weekly for 4 weeks. Mice were subjected to different cellular depletion and Fc receptor blocking strategies before challenge with peanut 1 week after the last sensitization. Results Our data indicate that pathways other than the classical mast cell (MC)–IgE pathway contribute to the full spectrum of anaphylactic reactions to peanut. We show that the single deletion of MCs, basophils, or phagocytes (ie, macrophages) prevents the most significant clinical outcome: death. Remarkably, the combined deficiency of MCs and phagocytes, but not MCs and basophils, averted nearly all clinical and physiological signs of anaphylaxis. Furthermore, blockade of both IgE and IgG1 signaling was necessary to abolish anaphylactic responses to peanut. Although MC responses occurred through IgE and IgG1, phagocyte responses were fully mediated through IgG1. Conclusions Peanut-induced anaphylaxis is a process that involves the concerted action of multiple immune effector pathways, and thus interventions targeting a single pathway (eg, MC-IgE) might not be sufficient to fully prevent anaphylactic responses.