title: Basophil-mediated protection against gastrointestinal helminths requires IgE-induced cytokine secretion.
abstract: 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.
authors.affiliation: Department of Infection Biology, Universitätsklinikum Erlangen, 91054 Erlangen, Germany; Department of Biology, Friedrich Alexander University Erlangen-Nürnberg, 91058 Erlangen, Germany;
authors.forename: Christian
authors.initials: C
authors.lastname: Schwartz
authors.affiliation: Department of Infection Biology, Universitätsklinikum Erlangen, 91054 Erlangen, Germany; Department of Biology, Friedrich Alexander University Erlangen-Nürnberg, 91058 Erlangen, Germany;
authors.forename: Adriana
authors.initials: A
authors.lastname: Turqueti-Neves
authors.affiliation: Institute of Immunology, Freie Universität Berlin, 14163 Berlin, Germany; and.
authors.forename: Susanne
authors.initials: S
authors.lastname: Hartmann
authors.affiliation: Institute for Immunology, Philipps-University Marburg, 35032 Marburg, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Yu
authors.affiliation: Department of Biology, Friedrich Alexander University Erlangen-Nürnberg, 91058 Erlangen, Germany;
authors.forename: Falk
authors.initials: F
authors.lastname: Nimmerjahn
authors.affiliation: Department of Infection Biology, Universitätsklinikum Erlangen, 91054 Erlangen, Germany; Department of Biology, Friedrich Alexander University Erlangen-Nürnberg, 91058 Erlangen, Germany; David.Voehringer@uk-erlangen.de.
authors.forename: David
authors.initials: D
authors.lastname: Voehringer
mesh_terms: D000818:Animals; D001491:Basophils / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D015153:Blotting, Western; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D041981:Gastrointestinal Tract / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D006369:Heligmosomatoidea / Q000276:immunology* / Q000502:physiology; D006790:Host-Parasite Interactions / Q000276:immunology; D007073:Immunoglobulin E / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018793:Interleukin-13 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007421:Intestine, Small / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009351:Nematospiroides dubius / Q000276:immunology / Q000502:physiology; D009559:Nippostrongylus / Q000276:immunology / Q000502:physiology; D011961:Receptors, Fc / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D017206:Strongylida Infections / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; D018793:Interleukin-13; D011961:Receptors, Fc; D015847:Interleukin-4; D007073:Immunoglobulin E
keywords: IL-4; IgE; basophils; helminths; protective immunity