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Tumour necrosis factor α restores granulomas and induces parasite egg-laying in schistosome-infected SCID mice

Nature volume 356, pages 604–607 (1992)Cite this article

Abstract

SCHISTOSOMIASIS (bilharzia) is a parasitic disease caused by several species of schistosome worms (blood flukes). The key pathogenic event in this disease is the formation of granulomas around schistosome eggs trapped in portal venules of the liver1–9. Granulomas are a distinctive form of chronic inflammation characterized by localized aggregation of activated macrophages around an inciting stimulus10. Each granuloma evolves to form a fibrous scar; in schistosomiasis, the result is widespread hepatic fibrosis and portal hypertension. To identify the specific immune signal molecules necessary for granuloma formation, we studied schistosome infections in severe combined immunodeficient (SCID) mice, which have normal macrophages but lack functional B or T lymphocytes11,12. Here we report that the immunoregulatory cytokine tumour necrosis factor α is necessary and sufficient to reconstitute granuloma formation in schistosome-infected SCID mice. Moreover, we find that the parasitic worms require tumour necrosis factor α for egg-laying and for excretion of eggs from the host. The implication of this latter result is that the parasite has adapted so successfully to its host that it uses a host-derived immuno-regulatory protein as a signal for replication and transmission.

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Authors and Affiliations

  1. Department of Pathology, University of California, San Francisco, California, 94143-0506, USA

    Payman Amiri, Tristram G. Parslow, Ernest Rector, Dianne Ritter & James H. McKerrow

  2. Department o Medicine, University of California, San Francisco, California, 94143-0506, USA

    Richard M. Locksley & Michael Sadickt

  3. Department of Microbiology and Immunology, University of California, San Francisco, California, 94143-0506, USA

    Richard M. Locksley & Tristram G. Parslow

  4. Department of Veterans Affairs Medical Center, Anatomic Pathology Service-113B, 4150 Clement Street, San Francisco, California, 94121, USA

    James H. McKerrow

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  1. Payman Amiri
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Amiri, P., Locksley, R., Parslow, T. et al. Tumour necrosis factor α restores granulomas and induces parasite egg-laying in schistosome-infected SCID mice. Nature 356, 604–607 (1992). https://doi.org/10.1038/356604a0

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