Antibodies and IL-3 support helminth-induced basophil expansion

Abstract

Basophils are powerful mediators of Th2 immunity and are present in increased numbers during allergic inflammation and helminth infection. Despite their ability to potentiate Th2 immunity the mechanisms regulating basophil development remain largely unknown. We have found a unique role for isotype-switched antibodies in promoting helminth-induced basophil production following infection of mice with Heligmosomoides polygyrus bakeri or Nippostrongylus brasiliensis . H. polygyrus bakeri -induced basophil expansion was found to occur within the bone marrow, and to a lesser extent the spleen, and was IL-3 dependent. IL-3 was largely produced by CD4 + CD49b + NK1.1 − effector T cells at these sites, and required the IL-4Rα chain. However, antibody-deficient mice exhibited defective basophil mobilization despite intact T-cell IL-3 production, and supplementation of mice with immune serum could promote basophilia independently of required IL-4Rα signaling. Helminth-induced eosinophilia was not affected by the deficiency in isotype-switched antibodies, suggesting a direct effect on basophils rather than through priming of Th2 responses. Although normal type 2 immunity occurred in the basopenic mice following primary infection with H. polygyrus bakeri , parasite rejection following challenge infection was impaired. These data reveal a role for isotype-switched antibodies in promoting basophil expansion and effector function following helminth infection.

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

“…This finding indicates that IgE mediates rapid worm expulsion and thereby limits the spread of the disease. FcRγ −/− mice were reported to lack basophilia in response to Hp infection, indicating that immune complexes act directly on basophils or their precursors to enhance proliferation and survival (18). However, our results challenge this concept, because we observed normal basophilia in FcRγ −/− mice, IgE ki/ki mice, and IgE −/− mice after Hp or Nb infection.…”

“…Basophil levels declined to basal levels 3 wk after infection in both KO and control mice, and we observed no differences during expansion after secondary infection. In contrast to a previous report (18), we also found unimpaired basophilia in FcRγ −/− mice (Fig. S5).…”

“…We and others have shown that basophils contribute to protective immune responses against secondary infection by Nb and ticks (13,14,17). Antibodymediated depletion of basophils also was reported to result in partially impaired protection against Hp and Trichuris muris (18,19). However, the mechanisms by which basophils mediate protection remained elusive.…”

Signaling pathways activated by a protease allergen in basophils

“…A similar concept is illustrated by a requirement for antigen-independent tonic signals through the B-cell receptor for B-cell development (41)(42)(43). It has been suggested that isotype-switched antibodies and FcRγ expression play a role in supporting Heligmosomoides polygyrus-induced expansion of basophils (44). This and other studies suggest that expression of FcRγ plays an instrumental role in basophil responses (24), and here we suggest an additional role for FcRγ that is independent of antibody binding.…”

Antibody-Mediated Trapping of Helminth Larvae Requires CD11b and Fcγ Receptor I

“…The striking role of the activating IgG receptor FcgRI (CD64) in larval immobilization by alternatively activated MF was unexpected due to the well-described involvement of this receptor in type 1 responses such as autoimmunity and protection against bacterial infection (35). Moreover, infection with the intestinal nematode H. polygyrus bakeri is associated with high levels of IgG1 in IS from challenge-infected or vaccinated mice, which has therefore been suggested to be the most relevant Ab isotype for protection (16,42,43). However, IgG1 or IgG1 immune complexes have been reported to bind to FcgRs II and III, but not FcgRI (30,44).…”