title: Helminth infection with Litomosoides sigmodontis induces regulatory T cells and inhibits allergic sensitization, airway inflammation, and hyperreactivity in a murine asthma model.
abstract: Numerous epidemiological studies have shown an inverse correlation between helminth infections and the manifestation of atopic diseases, yet the immunological mechanisms governing this phenomenon are indistinct. We therefore investigated the effects of infection with the filarial parasite Litomosoides sigmodontis on allergen-induced immune reactions and airway disease in a murine model of asthma. Infection with L. sigmodontis suppressed all aspects of the asthmatic phenotype: Ag-specific Ig production, airway reactivity to inhaled methacholine, and pulmonary eosinophilia. Similarly, Ag-specific recall proliferation and overall Th2 cytokine (IL-4, IL-5, and IL-3) production were significantly reduced after L. sigmodontis infection. Analysis of splenic mononuclear cells and mediastinal lymph nodes revealed a significant increase in the numbers of T cells with a regulatory phenotype in infected and sensitized mice compared with sensitized controls. Additionally, surface and intracellular staining for TGF-beta on splenic CD4(+) T cells as well as Ag-specific TGF-beta secretion by splenic mononuclear cells was increased in infected and sensitized animals. Administration of Abs blocking TGF-beta or depleting regulatory T cells in infected animals before allergen sensitization and challenges reversed the suppressive effect with regard to airway hyperreactivity, but did not affect airway inflammation. Despite the dissociate results of the blocking experiments, these data point toward an induction of regulatory T cells and enhanced secretion of the immunomodulatory cytokine TGF-beta as one principle mechanism. In conclusion, our data support the epidemiological evidence and enhance the immunological understanding concerning the impact of helminth infections on atopic diseases thus providing new insights for the development of future studies.
authors.affiliation: Department of Pediatric Pneumology and Immunology, Charité-Campus Virchow Klinikum, Universitätsmedizin in Berlin, Augustenburger Platz 1, Germany.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Dittrich
authors.forename: Annika
authors.initials: A
authors.lastname: Erbacher
authors.forename: Sabine
authors.initials: S
authors.lastname: Specht
authors.forename: Felix
authors.initials: F
authors.lastname: Diesner
authors.forename: Martin
authors.initials: M
authors.lastname: Krokowski
authors.forename: Angela
authors.initials: A
authors.lastname: Avagyan
authors.forename: Philippe
authors.initials: P
authors.lastname: Stock
authors.forename: Birgit
authors.initials: B
authors.lastname: Ahrens
authors.forename: Wolfgang H
authors.initials: WH
authors.lastname: Hoffmann
authors.forename: Achim
authors.initials: A
authors.lastname: Hoerauf
authors.forename: Eckard
authors.initials: E
authors.lastname: Hamelmann
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D000909:Antibodies, Helminth / Q000276:immunology; D001249:Asthma / Q000150:complications / Q000276:immunology*; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D005368:Filariasis / Q000150:complications / Q000276:immunology*; D007136:Immunoglobulins / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000037:antagonists & inhibitors; D051379:Mice; D008807:Mice, Inbred BALB C; D010641:Phenotype; D012130:Respiratory Hypersensitivity / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016211:Transforming Growth Factor alpha / Q000037:antagonists & inhibitors
chemical_list: D000485:Allergens; D019138:Antibodies, Blocking; D000909:Antibodies, Helminth; D016207:Cytokines; D007136:Immunoglobulins; D053645:Interleukin-2 Receptor alpha Subunit; D016211:Transforming Growth Factor alpha