IgE antibodies, FcεRIα, and IgE-mediated local anaphylaxis can limit snake venom toxicity

• Published in: Journal of allergy and clinical immunology 2016-01, Vol.137 (1), p.246-257.e11
• Main Authors: Starkl, Philipp, PhD, Marichal, Thomas, DVM, PhD, Gaudenzio, Nicolas, PhD, Reber, Laurent Lionel, PhD, Sibilano, Riccardo, PhD, Tsai, Mindy, DMSc, Galli, Stephen Joseph, MD
• Format: Article
• Language: English
• Subjects: Acquired resistance; allergy; Allergy and Immunology; Anaphylaxis - immunology; Animals; Apis mellifera; Bee Venoms - immunology; Cell Degranulation; Daboia russelii; FcεRIα; Female; honeybee; IgE; Immunization; Immunoglobulin E - immunology; Immunology; Life Sciences; mast cells; Mast Cells - immunology; Mast Cells - physiology; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Transgenic; Receptors, IgE - genetics; Receptors, IgE - immunology; Russell viper; toxin hypothesis; type 2 immunity; venom; Viper Venoms - immunology
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2015.08.005

Background Type 2 cytokine–related immune responses associated with development of antigen-specific IgE antibodies can contribute to pathology in patients with allergic diseases and to fatal anaphylaxis. However, recent findings in mice indicate that IgE also can enhance defense against honeybee venom. Objective We tested whether IgE antibodies, IgE-dependent effector mechanisms, and a local anaphylactic reaction to an unrelated antigen can enhance defense against Russell viper venom (RVV) and determined whether such responses can be influenced by immunization protocol or mouse strain. Methods We compared the resistance of RVV-immunized wild-type, IgE-deficient, and Fcer1a -deficient mice after injection of a potentially lethal dose of RVV. Results A single prior exposure to RVV enhanced the ability of wild-type mice, but not mice lacking IgE or functional FcεRI, to survive challenge with a potentially lethal amount of RVV. Moreover, IgE-dependent local passive cutaneous anaphylaxis in response to challenge with an antigen not naturally present in RVV significantly enhanced resistance to the venom. Finally, we observed different effects on resistance to RVV or honeybee venom in BALB/c versus C57BL/6 mice that had received a second exposure to that venom before challenge with a high dose of that venom. Conclusion These observations illustrate the potential benefit of IgE-dependent effector mechanisms in acquired host defense against venoms. The extent to which type 2 immune responses against venoms can decrease pathology associated with envenomation seems to be influenced by the type of venom, the frequency of venom exposure, and the genetic background of the host.