Antibodies and IL-3 support helminth-induced basophil expansion.

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.

Citation

Tina Herbst, Julia Esser, Moira Prati, Manuel Kulagin, Rebecca Stettler, Mario M Zaiss, James P Hewitson, Patrick Merky, Joseph S Verbeek, Carole Bourquin, Mali Camberis, Melanie Prout, Rick M Maizels, Graham Le Gros, Nicola L Harris. Antibodies and IL-3 support helminth-induced basophil expansion. Proceedings of the National Academy of Sciences of the United States of America. 2012 Sep 11;109(37):14954-9

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PMID: 22930820

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