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

Article metrics

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.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1

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

  2. 2

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

  3. 3

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

  4. 4

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

  5. 5

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

  6. 6

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

  7. 7

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

  8. 8

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

  9. 9

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

  10. 10

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

  11. 11

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

  12. 12

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

  13. 13

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

  14. 14

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

  15. 15

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

  16. 16

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

  17. 17

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

  18. 18

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

  19. 19

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

  20. 20

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

  21. 21

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

  22. 22

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

  23. 23

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

  24. 24

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

  25. 25

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

  26. 26

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

  27. 27

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

Download references

Author information

Rights and permissions

Reprints and Permissions

About this article

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.