Basophil-mediated protection against gastrointestinal helminths requires IgE-induced cytokine secretion

Significance Gastrointestinal worms (helminths) infect more than 2 billion people, and vaccines are not yet available. Helminths elicit a type 2 immune response characterized by high serum IgE levels and increased numbers of IL-4– or IL-13–secreting effector cells including Th2 cells, eosinophils, basophils, and type 2 innate lymphoid cells. We determined the mechanism by which basophils contribute to protection against secondary infections with gastrointestinal helminths. Here we demonstrate that basophils are recruited into the small intestine of infected mice and orchestrate the local type 2 immune response in this tissue. Basophil-mediated protection required the presence of IgE and the expression of activating Fc receptors and IL-4/IL-13 in basophils. These findings could help the development of new vaccination strategies against helminths. Basophils orchestrate protection against reinfections with gastrointestinal helminths and ticks, but the underlying mechanisms remain elusive. We investigated the role of Fc receptors on basophils, the antibody isotypes IgG1 and IgE, and basophil-derived IL-4/IL-13 during challenge infections with Heligmosomoides polygyrus and Nippostrongylus brasiliensis . Using mixed bone marrow chimeras, we found that activating Fc receptors on basophils were required for protective immunity but not for regulation of basophil homeostasis. Furthermore, rapid worm expulsion was impaired in IgE-deficient but not in IgG1-deficient mice. Basophils promoted the recruitment of other effector cells into the small intestine and induced expression of the antihelminthic proteins resistin-like molecule β and mucin 5ac. Selective deletion of IL-4/IL-13 in basophils resulted in impaired worm expulsion. Collectively, our results indicate that IgE-mediated activation of basophils and the release of basophil-derived IL-4/IL-13 are critical steps in protective immunity against helminths. Therefore, development of effective vaccines against helminths should consider boosting the IL-4/IgE/basophil axis of the immune system.