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

Research output: Contribution to journalArticleResearchpeer-review

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

Cite this

Esser-Von Bieren, J., Volpe, B., Kulagin, M., Sutherland, D. B., Guiet, R., Seitz, A., ... 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
Esser-Von Bieren, Julia ; Volpe, Beatrice ; Kulagin, Manuel ; Sutherland, Duncan B. ; Guiet, Romain ; Seitz, Arne ; Marsland, Benjamin J. ; Verbeek, J. Sjef ; Harris, Nicola L. / Antibody-mediated trapping of helminth larvae requires CD11b and fcg receptor I. In: Journal of Immunology. 2015 ; Vol. 194, No. 3. pp. 1154-1163.
@article{96a310bf011a4fb0b86dd3af8a772d9c,
title = "Antibody-mediated trapping of helminth larvae requires CD11b and fcg receptor I",
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.",
author = "{Esser-Von Bieren}, Julia and Beatrice Volpe and Manuel Kulagin and Sutherland, {Duncan B.} and Romain Guiet and Arne Seitz and Marsland, {Benjamin J.} and Verbeek, {J. Sjef} and Harris, {Nicola L.}",
year = "2015",
month = "2",
day = "1",
doi = "10.4049/jimmunol.1401645",
language = "English",
volume = "194",
pages = "1154--1163",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "3",

}

Esser-Von Bieren, J, Volpe, B, Kulagin, M, Sutherland, DB, Guiet, R, Seitz, A, Marsland, BJ, Verbeek, JS & Harris, NL 2015, 'Antibody-mediated trapping of helminth larvae requires CD11b and fcg receptor I' Journal of Immunology, vol. 194, no. 3, pp. 1154-1163. https://doi.org/10.4049/jimmunol.1401645

Antibody-mediated trapping of helminth larvae requires CD11b and fcg receptor I. / Esser-Von Bieren, Julia; Volpe, Beatrice; Kulagin, Manuel; Sutherland, Duncan B.; Guiet, Romain; Seitz, Arne; Marsland, Benjamin J.; Verbeek, J. Sjef; Harris, Nicola L.

In: Journal of Immunology, Vol. 194, No. 3, 01.02.2015, p. 1154-1163.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Antibody-mediated trapping of helminth larvae requires CD11b and fcg receptor I

AU - Esser-Von Bieren, Julia

AU - Volpe, Beatrice

AU - Kulagin, Manuel

AU - Sutherland, Duncan B.

AU - Guiet, Romain

AU - Seitz, Arne

AU - Marsland, Benjamin J.

AU - Verbeek, J. Sjef

AU - Harris, Nicola L.

PY - 2015/2/1

Y1 - 2015/2/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84921495241&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.1401645

DO - 10.4049/jimmunol.1401645

M3 - Article

VL - 194

SP - 1154

EP - 1163

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 3

ER -

Esser-Von Bieren J, Volpe B, Kulagin M, Sutherland DB, Guiet R, Seitz A et al. Antibody-mediated trapping of helminth larvae requires CD11b and fcg receptor I. Journal of Immunology. 2015 Feb 1;194(3):1154-1163. https://doi.org/10.4049/jimmunol.1401645