Skip to main content

Advertisement

SpringerLink
Log in

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

  • Letter
  • Published:

From Nature

View current issue Submit your manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Warren, K. S., Domingo, E. O. & Cowan, R. B. T. Am. J. Path. 51, 735–756 (1967).

    CAS  PubMed  Google Scholar 

  2. Phillips, S. M. & Colley, D. G. Prog. Allergy 24, 49–182 (1978).

    CAS  PubMed  Google Scholar 

  3. Doughty, B. L. & Phillips, S. M. J. Immun. 128, 37–42 (1982).

    CAS  PubMed  Google Scholar 

  4. Prakash, S., Postlethwaite, A. E., Stricklin, G. P. & Wyler, D. J. J. Immun. 144, 317–322 (1990).

    CAS  PubMed  Google Scholar 

  5. Olds, G. R. & Kresina, T. F. J. infect. Dis. 159, 798–801 (1989).

    Article  CAS  Google Scholar 

  6. Byram, J. E. & von Lichtenberg, F. Am. J. trop. Med. Hyg. 26, 944–955 (1977).

    Article  CAS  Google Scholar 

  7. Cheever, A. W., Byram, J. E. & von Lichtenberg, F. Parasite Immun. 7, 387–398 (1985).

    Article  CAS  Google Scholar 

  8. Cheever, A. W., Deb, S. & Duvall, R. H. Am. J. trop. Med. Hyg. 40, 66–71 (1989).

    Article  CAS  Google Scholar 

  9. Mathew, R. C. & Boros, D. L. Infect. Immunity. 54, 820–826 (1986).

    CAS  Google Scholar 

  10. Robbins, S. L., Cotran, R. S. & Kumar, V. Pathologic Basis of Disease 64–65 (Saunders, Philadelphia, 1984).

    Google Scholar 

  11. Bosma, G. C., Custer, R. P. & Bosma, M. J. Nature 301, 527–530 (1983).

    Article  ADS  CAS  Google Scholar 

  12. Custer, R. P., Bosma, G. C. & Bosma, M. J. Am. J. Path. 120, 464–477 (1985).

    CAS  PubMed  Google Scholar 

  13. Pearce, E. J., Caspar, P., Grzych, J. M., Lewis, F. A. & Sher, A. J. exp. Med. 173, 159–166 (1991).

    Article  CAS  Google Scholar 

  14. Grzych, J. M. et al. Immun. 146, 1322–1327 (1991).

    CAS  Google Scholar 

  15. McGee, H. J., Long, S. R. & Briggs, W. R. Nature 308, 667–668 (1984).

    Article  ADS  CAS  Google Scholar 

  16. Kaye, J. & Janeway, C. A. J. exp. Med. 159, 1397–1412 (1984).

    Article  CAS  Google Scholar 

  17. Chensue, S. W., Otterness, I. G., Higashi, G. I., Forsch, C. S. & Kunkel, S. L. J. Immun. 142, 1281–1286 (1989).

    CAS  PubMed  Google Scholar 

  18. Kindler, V., Sappino, A.-P., Grau, G. E., Piguet, P.-F. & Vassalli, P. Cell 56, 731–740 (1989).

    Article  CAS  Google Scholar 

  19. Jäätelä, M. Lab. Invest. 64, 724–742 (1991).

    Google Scholar 

  20. Piguet, P. F., Collart, M. A., Grau, G. E., Sappino, A.-P. & Vassalli, P. Nature 344, 245–247 (1990).

    Article  ADS  CAS  Google Scholar 

  21. Byram, J. E., Doenhoff, M. J., Musallam, R., Brink, L. H. & von Lichtenberg, F. Am. J. trop. Med. Hyg. 28, 274–285 (1979).

    Article  CAS  Google Scholar 

  22. Doenhoff, M. J., Dunne, D. W., Bain, J., Lillywhite, J. E. & McLaren, M. L. Devl. Biol. Standard. 62, 63–73 (1985).

    CAS  Google Scholar 

  23. Perrin, P. J. & Phillips, S. M. J. Immun. 141, 1714–1719 (1988).

    CAS  PubMed  Google Scholar 

  24. Doenhoff, M. J., Hassounah, O. & Murare, H. Trans. R. Soc. trop. Med. Hyg. 80, 503–514 (1986).

    Article  CAS  Google Scholar 

  25. Duvall, R. H. & DeWitt, W. B. Am. J. trop. Med. Hyg. 16, 483–486 (1967).

    Article  CAS  Google Scholar 

  26. Cheever, A. W., Deb, S. & Duvall, R. H. Am. J. trop. Med. Hyg. 40, 66–71 (1989).

    Article  CAS  Google Scholar 

  27. Basch, P. F. J. Parasit. 67, 179–185 (1981).

    Article  CAS  Google Scholar 

Download references

Author information

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

Authors
  1. Payman Amiri
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Richard M. Locksley
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tristram G. Parslow
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michael Sadickt
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ernest Rector
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Dianne Ritter
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. James H. McKerrow
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/356604a0

  • Springer Nature Limited

This article is cited by

Search

Navigation