Antibody-mediated trapping of helminth larvae requires CD11b and fcg receptor I

Julia Esser-Von Bieren, Beatrice Volpe, Manuel Kulagin, Duncan B. Sutherland, Romain Guiet, Arne Seitz, Benjamin J. Marsland, J. Sjef Verbeek, Nicola L. Harris

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13 Citations (Scopus)

Abstract

Infections with intestinal helminths severely impact on human and veterinary health, particularly through the damage that these large parasites inflict when migrating through host tissues. Host immunity often targets the motility of tissue-migrating helminth larvae, which ideally should be mimicked by anti-helminth vaccines. However, the mechanisms of larval trapping are still poorly defined. We have recently reported an important role for Abs in the rapid trapping of tissue-migrating larvae of the murine parasite Heligmosomoides polygyrus bakeri. Trapping was mediated by macrophages (MF) and involved complement, activating FcRs, and Arginase-1 (Arg1) activity. However, the receptors and Ab isotypes responsible for MF adherence and Arg1 induction remained unclear. Using an in vitro coculture assay of H. polygyrus bakeri larvae and bone marrow-derived MF, we now identify CD11b as the major complement receptor mediating MF adherence to the larval surface. However, larval immobilization was largely independent of CD11b and instead required the activating IgG receptor FcgRI (CD64) both in vitro and during challenge H. polygyrus bakeri infection in vivo. FcgRI signaling also contributed to the upregulation of MF Arg1 expression in vitro and in vivo. Finally, IgG2a/c was the major IgG subtype from early immune serum bound by FcgRI on the MF surface, and purified IgG2c could trigger larval immobilization and Arg1 expression in MF in vitro. Our findings reveal a novel role for IgG2a/c-FcgRI-driven MF activation in the efficient trapping of tissue-migrating helminth larvae and thus provide important mechanistic insights vital for anti-helminth vaccine development.

Original languageEnglish
Pages (from-to)1154-1163
Number of pages10
JournalJournal of Immunology
Volume194
Issue number3
DOIs
Publication statusPublished - 1 Feb 2015
Externally publishedYes

Cite this

Esser-Von Bieren, J., Volpe, B., Kulagin, M., Sutherland, D. B., Guiet, R., Seitz, A., Marsland, B. J., Verbeek, J. S., & Harris, N. L. (2015). Antibody-mediated trapping of helminth larvae requires CD11b and fcg receptor I. Journal of Immunology, 194(3), 1154-1163. https://doi.org/10.4049/jimmunol.1401645