title: Antibody-mediated trapping of helminth larvae requires CD11b and Fcγ 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 (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.
authors.affiliation: Swiss Vaccine Research Institute, Global Health Institute, Swiss Federal Institute of Technology, Lausanne, 1015 Lausanne, Switzerland;
authors.forename: Julia
authors.initials: J
authors.lastname: Esser-von Bieren
authors.affiliation: Swiss Vaccine Research Institute, Global Health Institute, Swiss Federal Institute of Technology, Lausanne, 1015 Lausanne, Switzerland;
authors.forename: Beatrice
authors.initials: B
authors.lastname: Volpe
authors.affiliation: Swiss Vaccine Research Institute, Global Health Institute, Swiss Federal Institute of Technology, Lausanne, 1015 Lausanne, Switzerland;
authors.forename: Manuel
authors.initials: M
authors.lastname: Kulagin
authors.affiliation: Swiss Vaccine Research Institute, Global Health Institute, Swiss Federal Institute of Technology, Lausanne, 1015 Lausanne, Switzerland;
authors.forename: Duncan B
authors.initials: DB
authors.lastname: Sutherland
authors.affiliation: Bioimaging and Optics Core Facility, Swiss Federal Institute of Technology, Lausanne, 1015 Lausanne, Switzerland;
authors.forename: Romain
authors.initials: R
authors.lastname: Guiet
authors.affiliation: Bioimaging and Optics Core Facility, Swiss Federal Institute of Technology, Lausanne, 1015 Lausanne, Switzerland;
authors.forename: Arne
authors.initials: A
authors.lastname: Seitz
authors.affiliation: Faculty of Biology and Medicine, Respiratory Division, University Hospital, Vaud, University of Lausanne, 1011 Lausanne, Switzerland; and.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Marsland
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, 2300 RC Leiden, the Netherlands.
authors.forename: J Sjef
authors.initials: JS
authors.lastname: Verbeek
authors.affiliation: Swiss Vaccine Research Institute, Global Health Institute, Swiss Federal Institute of Technology, Lausanne, 1015 Lausanne, Switzerland; nicola.harris@epfl.ch.
authors.forename: Nicola L
authors.initials: NL
authors.lastname: Harris
mesh_terms: D000818:Animals; D000909:Antibodies, Helminth / Q000276:immunology*; D001119:Arginase / Q000235:genetics / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism*; D003165:Complement System Proteins / Q000276:immunology / Q000378:metabolism; D015870:Gene Expression; D006374:Helminthiasis, Animal / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D006376:Helminths / Q000276:immunology*; D007106:Immune Sera / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D000067596:Interleukin-33; D007378:Interleukins / Q000378:metabolism; D007814:Larva; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D018345:Mice, Knockout; D008954:Models, Biological; D011485:Protein Binding; D017452:Receptors, IgG / Q000378:metabolism*; D019948:Receptors, Interleukin-4 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000909:Antibodies, Helminth; D039481:CD11b Antigen; C506535:Il33 protein, mouse; D007106:Immune Sera; D007074:Immunoglobulin G; D000067596:Interleukin-33; D007378:Interleukins; D017452:Receptors, IgG; D019948:Receptors, Interleukin-4; D003165:Complement System Proteins; C544448:Arg1 protein, mouse; D001119:Arginase