The immunobiology of schistosomiasis
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Chiaramonte, M. G., Donaldson, D. D., Cheever, A. W. & Wynn, T. A. An IL-13 inhibitor blocks the development of hepatic fibrosis during a T-helper type-2-dominated inflammatory response. J. Clin. Invest. 104, 777–785 (1999).This report established IL-13 as a profibrogenic mediator in schistosomiasis, and it describes a rationally designed experimental immunotherapy that blocks fibrosis.
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Dessein, A. J. et al. Severe hepatic fibrosis in Schistosoma mansoni infection is controlled by a major locus that is closely linked to the interferon-γ receptor gene. Am. J. Hum. Genet. 65, 709–721 (1999).Severe schistosomiasis occurs in less than 10% of infected individuals. This report is an important step towards understanding the genetic predispostion to severe disease.
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Bosshardt, S. C., Freeman, G. L. Jr, Secor, W. E. & Colley, D. G. IL-10 deficit correlates with chronic, hypersplenomegaly syndrome in male CBA/J mice infected with Schistosoma mansoni. Parasite Immunol. 19, 347–353 (1997).
Montesano, M. A., Colley, D. G., Eloi-Santos, S., Freeman, G. L. Jr & Secor, W. E. Neonatal idiotypic exposure alters subsequent cytokine, pathology and survival patterns in experimental Schistosoma mansoni infections. J. Exp. Med. 189, 637–645 (1999).
Hoffmann, K. F., Cheever, A. W. & Wynn, T. A. IL-10 and the dangers of immune polarization: excessive type 1 and type 2 cytokine responses induce distinct forms of lethal immunopathology in murine schistosomiasis. J. Immunol. 164, 6406–6416 (2000).This study establishes the immunological requirements for minimizing disease during the acute and chronic phases of schistosomiasis.
Vaillant, B., Chiaramonte, M. G., Cheever, A. W., Soloway, P. D. & Wynn, T. A. Regulation of hepatic fibrosis and extracellular matrix genes by the TH response: new insight into the role of tissue inhibitors of matrix metalloproteinases. J. Immunol. 167, 7017–7026 (2001).
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Rutitzky, L. I., Hernandez, H. J. & Stadecker, M. J. TH1-polarizing immunization with egg antigens correlates with severe exacerbation of immunopathology and death in schistosome infection. Proc. Natl Acad. Sci. USA 98, 13243–13248 (2001).References 33 and 34 show that induced T H 1 responses against egg antigens can lead to reduced hepatic fibrosis, but that there is a risk of severe disease in mice that are immunologically polarized in this way. These papers emphasize the importance of the appropriate immunological balance for optimal outcome during infection.
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Davies, S. J. et al. Modulation of blood-fluke development in the liver by hepatic CD4+ lymphocytes. Science 294, 1358–1361 (2001).This study expands on previous reports that schistosomes fail to develop properly in hosts that lack T cells. It raises many unanswered questions about the role of the previously unidentified CD4+ subset of hepatic lymphocytes that seems to have an important role in this process, and the identity of the mediator they produce that is used by the parasites.
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Beall, M. J. & Pearce, E. J. Human transforming growth factor-β activates a receptor serine/threonine kinase from the intravascular parasite Schistosoma mansoni. J. Biol. Chem. 276, 31613–31619 (2001).
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