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

  • Esser-von Bieren J Swiss Vaccine Research Institute, Global Health Institute, Swiss Federal Institute of Technology, Lausanne, 1015 Lausanne, Switzerland;
  • Volpe B Swiss Vaccine Research Institute, Global Health Institute, Swiss Federal Institute of Technology, Lausanne, 1015 Lausanne, Switzerland;
  • Kulagin M Swiss Vaccine Research Institute, Global Health Institute, Swiss Federal Institute of Technology, Lausanne, 1015 Lausanne, Switzerland;
  • Sutherland DB Swiss Vaccine Research Institute, Global Health Institute, Swiss Federal Institute of Technology, Lausanne, 1015 Lausanne, Switzerland;
  • Guiet R Bioimaging and Optics Core Facility, Swiss Federal Institute of Technology, Lausanne, 1015 Lausanne, Switzerland;
  • Seitz A Bioimaging and Optics Core Facility, Swiss Federal Institute of Technology, Lausanne, 1015 Lausanne, Switzerland;
  • Marsland BJ Faculty of Biology and Medicine, Respiratory Division, University Hospital, Vaud, University of Lausanne, 1011 Lausanne, Switzerland; and.
  • Verbeek JS Department of Human Genetics, Leiden University Medical Center, 2300 RC Leiden, the Netherlands.
  • Harris NL Swiss Vaccine Research Institute, Global Health Institute, Swiss Federal Institute of Technology, Lausanne, 1015 Lausanne, Switzerland; nicola.harris@epfl.ch.
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  • 2014-12-31
Published in:
  • Journal of immunology (Baltimore, Md. : 1950). - 2015
Animals
Antibodies, Helminth
Arginase
CD11b Antigen
Complement System Proteins
Gene Expression
Helminthiasis, Animal
Helminths
Immune Sera
Immunoglobulin G
Interleukin-33
Interleukins
Larva
Macrophage Activation
Macrophages
Mice, Knockout
Models, Biological
Protein Binding
Receptors, IgG
Receptors, Interleukin-4
Signal Transduction
English 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 (MΦ) and involved complement, activating FcRs, and Arginase-1 (Arg1) activity. However, the receptors and Ab isotypes responsible for MΦ adherence and Arg1 induction remained unclear. Using an in vitro coculture assay of H. polygyrus bakeri larvae and bone marrow-derived MΦ, we now identify CD11b as the major complement receptor mediating MΦ adherence to the larval surface. However, larval immobilization was largely independent of CD11b and instead required the activating IgG receptor FcγRI (CD64) both in vitro and during challenge H. polygyrus bakeri infection in vivo. FcγRI signaling also contributed to the upregulation of MΦ Arg1 expression in vitro and in vivo. Finally, IgG2a/c was the major IgG subtype from early immune serum bound by FcγRI on the MΦ surface, and purified IgG2c could trigger larval immobilization and Arg1 expression in MΦ in vitro. Our findings reveal a novel role for IgG2a/c-FcγRI-driven MΦ activation in the efficient trapping of tissue-migrating helminth larvae and thus provide important mechanistic insights vital for anti-helminth vaccine development.
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  • English
Open access status
bronze
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https://sonar.ch/global/documents/27321
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