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Immunopathogenesis of schistosomiasis

Authors

  • Thomas A. Wynn,

    Corresponding author
    1. Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
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  • Robert W. Thompson,

    1. Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
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  • Allen W. Cheever,

    1. Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
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  • Margaret M. Mentink-Kane

    1. Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
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* Thomas A Wynn
Laboratory of Parasitic Diseases
National Institute of Allergy and Infectious Diseases
National Institutes of Health
50 South Drive
Room 6154, MSC 8003
Bethesda, MD 20892
USA
Tel.: +1-301-496-4758
Fax: +1-301-480-5025
E-mail: twynn@niaid.nih.gov

Abstract

Summary:  In schistosomiasis mansoni, the chronic egg-induced granulomatous response in the liver and intestines may eventually cause extensive tissue scarring and development of portal hypertension. Indeed, much of the morbidity and mortality associated with this disease is directly attributable to the deposition of connective tissue elements in affected tissues. Elucidating the mechanisms that regulate the severity of schistosomiasis has been a major research objective over the past several years. Research conducted with DNA microarrays as well as investigations with a variety of gene knock-out mice have been particularly helpful in achieving this goal. A notable accomplishment in the past few years was the identification of interleukin-13 (IL-13) and the IL-13 receptor complex as central regulators of disease progression in schistosomiasis. Liver fibrogenesis is severely decreased in infected IL-13-deficient mice as well as in wildtype animals treated with IL-13 antagonists. In contrast, IL-13 effector function increases dramatically in IL-13 receptor α2 (IL-13Rα2)-deficient mice. These mice develop severe hepatic fibrosis, fail to downregulate granuloma formation in the chronic phase of S. mansoni infection, and succumb to the disease at an accelerated rate; thus, identifying the ‘decoy’ IL-13 receptor as a critical life sustaining ‘off’ switch for tissue damaging egg-induced inflammation.

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