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Allergies are considered to represent mal-directed type 2 immune responses against mostly innocuous exogenous compounds. Immunoglobulin E (IgE) antibodies are a characteristic feature of allergies and mediate hypersensitivity against allergens through activation of effector cells, particularly mast cells (MCs). Although the physiological functions of this dangerous branch of immunity have remained enigmatic, recent evidence shows that allergic immune reactions can help to protect against the toxicity of venoms. Because bacteria are a potent alternative source of toxins, we assessed the possible role of allergy-like type 2 immunity in antibacterial host defense. We discovered that the adaptive immune response against Staphylococcus aureus (SA) skin infection substantially improved systemic host defense against secondary SA infections in mice. Moreover, this acquired protection depended on IgE effector mechanisms and MCs. Importantly, our results reveal a previously unknown physiological function of allergic immune responses, IgE antibodies, and MCs in host defense against a pathogenic bacterium., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Allergies are widely considered to be misdirected type 2 immune responses, in which immunoglobulin E (IgE) antibodies are produced against any of a broad range of seemingly harmless antigens. However, components of insect venoms also can sensitize individuals to develop severe IgE-associated allergic reactions, including fatal anaphylaxis, upon subsequent venom exposure. We found that mice injected with amounts of honeybee venom similar to that which could be delivered in one or two stings developed a specific type 2 immune response that increased their resistance to subsequent challenge with potentially lethal amounts of the venom. Our data indicate that IgE antibodies and the high affinity IgE receptor, FcεRI, were essential for such acquired resistance to honeybee venom. The evidence that IgE-dependent immune responses against venom can enhance survival in mice supports the hypothesis that IgE, which also contributes to allergic disorders, has an important function in protection of the host against noxious substances., (Copyright © 2013 Elsevier Inc. All rights reserved.)