title: Oesophagostomum dentatum extract modulates T cell-dependent immune responses to bystander antigens and prevents the development of allergy in mice.
abstract: One third of the human population is currently infected by one or more species of parasitic helminths. Certain helminths establish long-term chronic infections resulting in a modulation of the host's immune system with attenuated responsiveness to "bystander" antigens such as allergens or vaccines. In this study we investigated whether parasite-derived products suppress the development of allergic inflammation in a mouse model. We show that extract derived from adult male Oesophagostomum dentatum (eMOD) induced Th2 and regulatory responses in BALB/c mice. Stimulation of bone marrow-derived dendritic cells induced production of regulatory cytokines IL-10 and TGF-beta. In a mouse model of birch pollen allergy, co-administration of eMOD with sensitizing allergen Bet v 1 markedly reduced the production of allergen-specific antibodies in serum as well as IgE-dependent basophil degranulation. Furthermore, eMOD prevented the development of airway inflammation, as demonstrated by attenuation of bronchoalveolar lavages eosinophil influx, peribronchial inflammatory infiltrate, and mucus secretion in lungs and IL-4 and IL-5 levels in lung cell cultures. Reduced secretion of Th2-related cytokines by birch pollen-re-stimulated splenocytes and mesenteric lymph node cells was observed in eMOD-treated/sensitized and challenged mice in comparison to sensitized and challenged controls. The suppressive effects of eMOD were heat-stable. Immunization with model antigens in the presence of eMOD reduced production of antibodies to thymus-dependent but not to thymus-independent antigen, suggesting that suppression of the immune responses by eMOD was mediated by interference with antigen presenting cell or T helper cell function but did not directly suppress B cell function. In conclusion, we have shown that eMOD possesses immunomodulatory properties and that heat-stable factors in eMOD are responsible for the dramatic suppression of allergic responses in a mouse model of type I allergy. The identification and characterization of parasite-derived immune-modulating molecules might have potential for designing novel prophylactic/therapeutic strategies for immune-mediated diseases.
authors.affiliation: Institute of Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria. irma.schabussova@meduniwien.ac.at
authors.forename: Irma
authors.initials: I
authors.lastname: Schabussova
authors.forename: Onisa
authors.initials: O
authors.lastname: Ul-Haq
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Hoflehner
authors.forename: Johnnie
authors.initials: J
authors.lastname: Akgün
authors.forename: Angelika
authors.initials: A
authors.lastname: Wagner
authors.forename: Gerhard
authors.initials: G
authors.lastname: Loupal
authors.forename: Anja
authors.initials: A
authors.lastname: Joachim
authors.forename: Bärbel
authors.initials: B
authors.lastname: Ruttkowski
authors.forename: Rick M
authors.initials: RM
authors.lastname: Maizels
authors.forename: Ursula
authors.initials: U
authors.lastname: Wiedermann
mesh_terms: D000485:Allergens / Q000008:administration & dosage / Q000276:immunology; D000818:Animals; D052179:Antigens, Plant / Q000008:administration & dosage / Q000276:immunology; D001491:Basophils / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D024201:Bystander Effect / Q000276:immunology; D045424:Complex Mixtures / Q000008:administration & dosage / Q000276:immunology* / Q000302:isolation & purification; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D007113:Immunity, Innate / Q000187:drug effects; D007073:Immunoglobulin E / Q000276:immunology; D056747:Immunomodulation; D016753:Interleukin-10 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009815:Oesophagostomum / Q000737:chemistry*; D011058:Pollen / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis
chemical_list: D000485:Allergens; D052179:Antigens, Plant; D045424:Complex Mixtures; D016212:Transforming Growth Factor beta; C061312:Bet v 1 allergen, Betula; D016753:Interleukin-10; D007073:Immunoglobulin E