Skip to main content
PMC home page
Infection and Immunity logoLink to Infection and Immunity
. 1996 Mar;64(3):744–750. doi: 10.1128/iai.64.3.744-750.1996

Plasmodium falciparum induces apoptosis in human mononuclear cells.

A Toure-Balde 1, J L Sarthou 1, G Aribot 1, P Michel 1, J F Trape 1, C Rogier 1, C Roussilhon 1
PMCID: PMC173832  PMID: 8641776

Abstract

The level of spontaneous apoptosis in short-term lymphocyte cultures was evaluated in different human immunodeficiency virus-negative groups of either healthy control individuals or patients with clinical malaria. The mean percentage of spontaneous apoptosis found in patients during a malaria attack was significantly higher than in sex- and age-matched healthy controls. The healthy asymptomatic controls were individuals with different degrees of exposure to Plasmodium falciparum as reflected by their various mean levels of specific anti-P. falciparum (immunoglobulin G and M) antibodies. The percentages of apoptotic nuclei were found to be significantly higher in lymphocytes from subjects living in an area where malaria is holoendemic than in lymphocytes from subjects less exposed. Concentrations of soluble plasma interleukin-2 receptor were also higher in subjects from areas where malaria is endemic than in other groups, revealing different levels of lymphocyte activation. Of particular relevance to the in vivo situation, a P. falciparum schizont-rich extract induced a systematic and significant elevation of apoptotic nuclei at day 6 in 87.5% (35 of 40) of the subjects tested. In additional studies with different concentrations of extract, [3H]thymidine incorporation was concomitant with a low or limited level of apoptosis. Taken together, our results strongly suggest that acute as well as chronic asymptomatic P. falciparum infections were consistently associated with a marked increase in the level of mononuclear cell apoptosis. This process could be implicated in some of the alterations reported for the proliferative T-cell responses in areas where malaria is endemic.

Full Text

The Full Text of this article is available as a PDF (264.4 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ameisen J. C., Capron A. Cell dysfunction and depletion in AIDS: the programmed cell death hypothesis. Immunol Today. 1991 Apr;12(4):102–105. doi: 10.1016/0167-5699(91)90092-8. [DOI] [PubMed] [Google Scholar]
  2. Arends M. J., Wyllie A. H. Apoptosis: mechanisms and roles in pathology. Int Rev Exp Pathol. 1991;32:223–254. doi: 10.1016/b978-0-12-364932-4.50010-1. [DOI] [PubMed] [Google Scholar]
  3. Baldé A. T., Sarthou J. L., Roussilhon C. Acute Plasmodium falciparum infection is associated with increased percentages of apoptotic cells. Immunol Lett. 1995 May;46(1-2):59–62. doi: 10.1016/0165-2478(95)00017-y. [DOI] [PubMed] [Google Scholar]
  4. Behr C., Dubois P. Preferential expansion of V gamma 9 V delta 2 T cells following stimulation of peripheral blood lymphocytes with extracts of Plasmodium falciparum. Int Immunol. 1992 Mar;4(3):361–366. doi: 10.1093/intimm/4.3.361. [DOI] [PubMed] [Google Scholar]
  5. Bursch W., Oberhammer F., Schulte-Hermann R. Cell death by apoptosis and its protective role against disease. Trends Pharmacol Sci. 1992 Jun;13(6):245–251. doi: 10.1016/0165-6147(92)90077-j. [DOI] [PubMed] [Google Scholar]
  6. Buttke T. M., Sandstrom P. A. Oxidative stress as a mediator of apoptosis. Immunol Today. 1994 Jan;15(1):7–10. doi: 10.1016/0167-5699(94)90018-3. [DOI] [PubMed] [Google Scholar]
  7. COHEN S., McGREGOR I. A., CARRINGTON S. Gamma-globulin and acquired immunity to human malaria. Nature. 1961 Nov 25;192:733–737. doi: 10.1038/192733a0. [DOI] [PubMed] [Google Scholar]
  8. Carson D. A., Ribeiro J. M. Apoptosis and disease. Lancet. 1993 May 15;341(8855):1251–1254. doi: 10.1016/0140-6736(93)91154-e. [DOI] [PubMed] [Google Scholar]
  9. Cohen J. J., Duke R. C., Fadok V. A., Sellins K. S. Apoptosis and programmed cell death in immunity. Annu Rev Immunol. 1992;10:267–293. doi: 10.1146/annurev.iy.10.040192.001411. [DOI] [PubMed] [Google Scholar]
  10. Deloron P., Lepers J. P., Coulanges P. Evolution of the levels of soluble interleukin-2 receptors during Plasmodium falciparum and P. vivax malaria. J Clin Microbiol. 1989 Aug;27(8):1887–1889. doi: 10.1128/jcm.27.8.1887-1889.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. DosReis G. A., Fonseca M. E., Lopes M. F. Programmed T-cell death in experimental chagas disease. Parasitol Today. 1995 Oct;11(10):391–394. doi: 10.1016/0169-4758(95)80011-5. [DOI] [PubMed] [Google Scholar]
  12. Gougeon M. L., Garcia S., Heeney J., Tschopp R., Lecoeur H., Guetard D., Rame V., Dauguet C., Montagnier L. Programmed cell death in AIDS-related HIV and SIV infections. AIDS Res Hum Retroviruses. 1993 Jun;9(6):553–563. doi: 10.1089/aid.1993.9.553. [DOI] [PubMed] [Google Scholar]
  13. Greenwood B. M., Vick R. M. Evidence for a malaria mitogen in human malaria. Nature. 1975 Oct 16;257(5527):592–594. doi: 10.1038/257592a0. [DOI] [PubMed] [Google Scholar]
  14. Groux H., Torpier G., Monté D., Mouton Y., Capron A., Ameisen J. C. Activation-induced death by apoptosis in CD4+ T cells from human immunodeficiency virus-infected asymptomatic individuals. J Exp Med. 1992 Feb 1;175(2):331–340. doi: 10.1084/jem.175.2.331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Haslett C. Resolution of acute inflammation and the role of apoptosis in the tissue fate of granulocytes. Clin Sci (Lond) 1992 Dec;83(6):639–648. doi: 10.1042/cs0830639. [DOI] [PubMed] [Google Scholar]
  16. Jakobsen P. H., Morris-Jones S., Theander T. G., Hviid L., Hansen M. B., Bendtzen K., Ridley R. G., Greenwood B. M. Increased plasma levels of soluble IL-2R are associated with severe Plasmodium falciparum malaria. Clin Exp Immunol. 1994 Apr;96(1):98–103. doi: 10.1111/j.1365-2249.1994.tb06237.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kabelitz D., Wesselborg S. Life and death of a superantigen-reactive human CD4+ T cell clone: staphylococcal enterotoxins induce death by apoptosis but simultaneously trigger a proliferative response in the presence of HLA-DR+ antigen-presenting cells. Int Immunol. 1992 Dec;4(12):1381–1388. doi: 10.1093/intimm/4.12.1381. [DOI] [PubMed] [Google Scholar]
  18. McCormack J. E., Callahan J. E., Kappler J., Marrack P. C. Profound deletion of mature T cells in vivo by chronic exposure to exogenous superantigen. J Immunol. 1993 May 1;150(9):3785–3792. [PubMed] [Google Scholar]
  19. Meyaard L., Otto S. A., Jonker R. R., Mijnster M. J., Keet R. P., Miedema F. Programmed death of T cells in HIV-1 infection. Science. 1992 Jul 10;257(5067):217–219. doi: 10.1126/science.1352911. [DOI] [PubMed] [Google Scholar]
  20. Molloy A., Laochumroonvorapong P., Kaplan G. Apoptosis, but not necrosis, of infected monocytes is coupled with killing of intracellular bacillus Calmette-Guérin. J Exp Med. 1994 Oct 1;180(4):1499–1509. doi: 10.1084/jem.180.4.1499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Nicoletti I., Migliorati G., Pagliacci M. C., Grignani F., Riccardi C. A rapid and simple method for measuring thymocyte apoptosis by propidium iodide staining and flow cytometry. J Immunol Methods. 1991 Jun 3;139(2):271–279. doi: 10.1016/0022-1759(91)90198-o. [DOI] [PubMed] [Google Scholar]
  22. Riley E. M., Andersson G., Otoo L. N., Jepsen S., Greenwood B. M. Cellular immune responses to Plasmodium falciparum antigens in Gambian children during and after an acute attack of falciparum malaria. Clin Exp Immunol. 1988 Jul;73(1):17–22. [PMC free article] [PubMed] [Google Scholar]
  23. Riley E. M., Rowe P., Allen S. J., Greenwood B. M. Soluble plasma IL-2 receptors and malaria. Clin Exp Immunol. 1993 Mar;91(3):495–499. doi: 10.1111/j.1365-2249.1993.tb05930.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Schmid I., Krall W. J., Uittenbogaart C. H., Braun J., Giorgi J. V. Dead cell discrimination with 7-amino-actinomycin D in combination with dual color immunofluorescence in single laser flow cytometry. Cytometry. 1992;13(2):204–208. doi: 10.1002/cyto.990130216. [DOI] [PubMed] [Google Scholar]
  25. Schmied M., Breitschopf H., Gold R., Zischler H., Rothe G., Wekerle H., Lassmann H. Apoptosis of T lymphocytes in experimental autoimmune encephalomyelitis. Evidence for programmed cell death as a mechanism to control inflammation in the brain. Am J Pathol. 1993 Aug;143(2):446–452. [PMC free article] [PubMed] [Google Scholar]
  26. Spencer H. C., Collins W. E., Chin W., Skinner J. C. The enzyme-linked immunosorbent assay (ELISA) for malaria. I. The use of in vitro-cultured Plasmodium falciparum as antigen. Am J Trop Med Hyg. 1979 Nov;28(6):927–932. doi: 10.4269/ajtmh.1979.28.927. [DOI] [PubMed] [Google Scholar]
  27. Theander T. G., Bygbjerg I. C., Andersen B. J., Jepsen S., Kharazmi A., Odum N. Suppression of parasite-specific response in Plasmodium falciparum malaria. A longitudinal study of blood mononuclear cell proliferation and subset composition. Scand J Immunol. 1986 Jul;24(1):73–81. doi: 10.1111/j.1365-3083.1986.tb02071.x. [DOI] [PubMed] [Google Scholar]
  28. Trager W., Jensen J. B. Human malaria parasites in continuous culture. Science. 1976 Aug 20;193(4254):673–675. doi: 10.1126/science.781840. [DOI] [PubMed] [Google Scholar]
  29. Trape J. F., Lefebvre-Zante E., Legros F., Ndiaye G., Bouganali H., Druilhe P., Salem G. Vector density gradients and the epidemiology of urban malaria in Dakar, Senegal. Am J Trop Med Hyg. 1992 Aug;47(2):181–189. doi: 10.4269/ajtmh.1992.47.181. [DOI] [PubMed] [Google Scholar]
  30. Trape J. F., Rogier C., Konate L., Diagne N., Bouganali H., Canque B., Legros F., Badji A., Ndiaye G., Ndiaye P. The Dielmo project: a longitudinal study of natural malaria infection and the mechanisms of protective immunity in a community living in a holoendemic area of Senegal. Am J Trop Med Hyg. 1994 Aug;51(2):123–137. doi: 10.4269/ajtmh.1994.51.123. [DOI] [PubMed] [Google Scholar]
  31. Uehara T., Miyawaki T., Ohta K., Tamaru Y., Yokoi T., Nakamura S., Taniguchi N. Apoptotic cell death of primed CD45RO+ T lymphocytes in Epstein-Barr virus-induced infectious mononucleosis. Blood. 1992 Jul 15;80(2):452–458. [PubMed] [Google Scholar]
  32. Voller A., Cornille-Brögger R., Storey J., Molineaux L. A longitudinal study of Plasmodium falciparum malaria in the West African savannah using the ELISA technique. Bull World Health Organ. 1980;58(3):429–438. [PMC free article] [PubMed] [Google Scholar]
  33. Wells R. A., Pavanand K., Zolyomi S., Permpanich B., MacDermott R. P. Loss of circulating T lymphocytes with normal levels of B and 'null' lymphocytes in Thai adults with malaria. Clin Exp Immunol. 1979 Feb;35(2):202–209. [PMC free article] [PubMed] [Google Scholar]
  34. Wyler D. J. Peripheral lymphocyte subpopulations in human falciparum malaria. Clin Exp Immunol. 1976 Mar;23(3):471–476. [PMC free article] [PubMed] [Google Scholar]
  35. Zychlinsky A., Prevost M. C., Sansonetti P. J. Shigella flexneri induces apoptosis in infected macrophages. Nature. 1992 Jul 9;358(6382):167–169. doi: 10.1038/358167a0. [DOI] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES