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* Department of Pediatric Pneumology and Immunology, Charité Universitätsmedizin in Berlin, Germany;
Institute for Tropical Medicine, Eberhard Karls University Tübingen, Germany; and
Institute of Medical Microbiology, Immunology, and Parasitology, University Clinic, Bonn, Germany
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-β on splenic CD4+ T cells as well as Ag-specific TGF-β secretion by splenic mononuclear cells was increased in infected and sensitized animals. Administration of Abs blocking TGF-β 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-β 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.
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1 This work was supported by the German National Genome Research Network (Nationales Genomforschungsnetz), by the German Ministry for Research (Bundesministerium für Bildung, Wissenschaft, Forschung und Technologie) to E.H. (01GS0120). A.E. and W.H.H. received financial support from the fortüne program of the University Hospital of Tübingen (Project 1247), by the International Cooperation with Developing Countries program of the European Union Commission (Contract ICA4-CT-1999-10002), and by the Nationale Genomforschungsnetz (01GSO114 and 01GSO403).
2 Current address: Collaborative Research Center 587 Immune Reactions of the Lunge in Infectious Diseases and Allergies, Medical School Hannover, 30625 Hannover, Germany.
3 Address correspondence and reprint requests to Dr. Eckard Hamelmann, Department of Pediatric Pneumonology and Immunology, Charité-Campus Virchow Klinikum, Universitätsmedizin in Berlin, Augustenburger Platz 1, 13353 Berlin, Germany. E-mail address: eckard.hamelmann{at}charite.de
4 Abbreviations used in this paper: AI, airway inflammation; AHR, airway hyperactivity, AR, airway reactivity; BAL, bronchoalveolar lavage; mLN, mediastinal lymph node; MNC, mononuclear cell; Treg, regulatory T cell; SS, systemic sensitization; DC, dendritic cell.
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