title: A helminth immunomodulator reduces allergic and inflammatory responses by induction of IL-10-producing macrophages.
abstract: The coincidence between infections with parasitic worms and the reduced prevalence of allergic disease in humans and in animal models has prompted the search for helminth molecules with antiallergic and antiinflammatory potential. We report herein that filarial cystatin, a secreted protease inhibitor of filarial nematodes, suppresses Th2-related inflammation and the ensuing asthmatic disease in a murine model of OVA-induced allergic airway responsiveness. Treatment with recombinant filarial cystatin inhibited eosinophil recruitment, reduced levels of OVA-specific and total IgE, down-regulated IL-4 production, and suppressed allergic airway hyperreactivity when applied during or after sensitization and before challenge with the allergen. Depletion of macrophages by clodronate-containing liposomes prevented the curative effects and restored the levels of infiltrating cells, IgE, and allergic airway reactivity. Blocking of IL-10 by application of anti-IL-10 receptor Abs restored the reduced number of infiltrating cells and the levels of OVA-specific IgE. In contrast, depletion of regulatory T cells by anti-CD25 Abs had only limited effects. Cystatin also modulated macrophage-mediated inflammation in a murine model of dextran sulfate sodium-induced colitis, leading to reduction of inflammatory infiltrations and epithelial damage. Our data demonstrate that treatment with a single helminth protein can exert the antiallergic effects of helminth infections.
authors.affiliation: Department of Molecular Parasitology, Humboldt University, Berlin, Germany.
authors.forename: Corinna
authors.initials: C
authors.lastname: Schnoeller
authors.forename: Sebastian
authors.initials: S
authors.lastname: Rausch
authors.forename: Smitha
authors.initials: S
authors.lastname: Pillai
authors.forename: Angela
authors.initials: A
authors.lastname: Avagyan
authors.forename: Bianca M
authors.initials: BM
authors.lastname: Wittig
authors.forename: Christoph
authors.initials: C
authors.lastname: Loddenkemper
authors.forename: Alf
authors.initials: A
authors.lastname: Hamann
authors.forename: Eckard
authors.initials: E
authors.lastname: Hamelmann
authors.forename: Richard
authors.initials: R
authors.lastname: Lucius
authors.forename: Susanne
authors.initials: S
authors.lastname: Hartmann
mesh_terms: D000208:Acute Disease; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D003092:Colitis / Q000276:immunology / Q000517:prevention & control; D015891:Cystatins / Q000502:physiology* / Q000627:therapeutic use; D004153:Dipetalonema / Q000276:immunology*; D005260:Female; D015801:Helminth Proteins / Q000627:therapeutic use; D007155:Immunologic Factors / Q000502:physiology*; D018836:Inflammation Mediators / Q000502:physiology; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000502:physiology; D008262:Macrophage Activation / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*
chemical_list: D015891:Cystatins; D015801:Helminth Proteins; D007155:Immunologic Factors; D018836:Inflammation Mediators; D016753:Interleukin-10