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. 1985 Jan;47(1):247–252. doi: 10.1128/iai.47.1.247-252.1985

Cytotoxicity of human serum for Leishmania donovani amastigotes: antibody facilitation of alternate complement pathway-mediated killing.

D L Hoover, M Berger, M H Oppenheim, W T Hockmeyer, M S Meltzer
PMCID: PMC261503  PMID: 3917426

Abstract

Mechanisms that mediate recovery from leishmanial infection have not been fully characterized but are generally believed to involve interactions between T lymphocytes and macrophages. A major role for serum-mediated effector mechanisms in the protection of humans from reinfection with Leishmania, however, has not been ruled out. In this report, amastigotes of L. donovani were incubated with dilutions of serum from normal subjects and from patients with kala-azar. Normal serum was cytotoxic for parasites at a dilution of greater than or equal to 1:20. Cytotoxicity did not occur in the presence of EDTA, was abolished by heating serum to 56 degrees C for 30 min, and was not diminished by prior adsorption of normal serum with parasites at 0 degree C. Killing proceeded normally in the presence of magnesium-ethylene glycol-bis(beta-aminoethyl ether)-N, N-tetraacetic acid, however, and was fully effected by C2-deficient serum. These studies indicated that killing of amastigotes, unlike that of promastigotes, was mediated via the alternate pathway of serum complement. In further studies, cytotoxicity of normal serum was enhanced three- to fivefold by factors in patient serum. This enhanced cytotoxicity also proceeded via the alternate complement pathway. Factors that enhanced cytotoxicity were characterized as parasite-specific immunoglobulin G: they eluted with immunoglobulin G on column chromatography, were adsorbed by immobilized staphylococcal protein A, and were not removed from the parasite surface by extensive washing. Thus, infection of individuals with L. donovani resulted in the production of a new, qualitatively and quantitatively distinct immune mechanism directed against the amastigote form of the parasite, namely, antibody-directed, alternate complement pathway-mediated cytotoxicity. These results provide a mechanistic framework for a role of humoral factors in human resistance to reinfection with L. donovani.

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Selected References

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  1. Brunell P. A., Gershon A. A., Hughes W. T., Riley H. D., Jr, Smith J. Prevention of varicella in high risk children: a collaborative study. Pediatrics. 1972 Nov;50(5):718–722. [PubMed] [Google Scholar]
  2. Cunningham I. New culture medium for maintenance of tsetse tissues and growth of trypanosomatids. J Protozool. 1977 May;24(2):325–329. doi: 10.1111/j.1550-7408.1977.tb00987.x. [DOI] [PubMed] [Google Scholar]
  3. Dolin R., Reichman R. C., Mazur M. H., Whitley R. J. NIH conference. Herpes zoster-varicella infections in immunosuppressed patients. Ann Intern Med. 1978 Sep;89(3):375–388. doi: 10.7326/0003-4819-89-3-375. [DOI] [PubMed] [Google Scholar]
  4. Dwyer D. M. Antibody-induced modulation of Leishmania donovani surface membrane antigens. J Immunol. 1976 Dec;117(6):2081–2091. [PubMed] [Google Scholar]
  5. Hoover D. L., Berger M., Nacy C. A., Hockmeyer W. T., Meltzer M. S. Killing of Leishmania tropica amastigotes by factors in normal human serum. J Immunol. 1984 Feb;132(2):893–897. [PubMed] [Google Scholar]
  6. Hoover D. L., Nacy C. A. Analysis of macrophage interactions with cryopreserved amastigotes of Leishmania tropica. Infect Immun. 1983 Sep;41(3):1363–1367. doi: 10.1128/iai.41.3.1363-1367.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Joiner K. A., Goldman R. C., Hammer C. H., Leive L., Frank M. M. Studies on the mechanism of bacterial resistance to complement-mediated killing. VI. IgG increases the bactericidal efficiency of C5b-9 for E. coli 0111B4 by acting at a step before C5 cleavage. J Immunol. 1983 Nov;131(5):2570–2575. [PubMed] [Google Scholar]
  8. Nacy C. A., Meltzer M. S., Leonard E. J., Wyler D. J. Intracellular replication and lymphokine-induced destruction of Leishmania tropica in C3H/HeN mouse macrophages. J Immunol. 1981 Dec;127(6):2381–2386. [PubMed] [Google Scholar]
  9. Pearson R. D., Steigbigel R. T. Mechanism of lethal effect of human serum upon Leishmania donovani. J Immunol. 1980 Nov;125(5):2195–2201. [PubMed] [Google Scholar]
  10. Preston P. M., Dumonde D. C. Experimental cutaneous leishmaniasis. V. Protective immunity in subclinical and self-healing infection in the mouse. Clin Exp Immunol. 1976 Jan;23(1):126–138. [PMC free article] [PubMed] [Google Scholar]
  11. Rezai H. R., Farrell J., Soulsby E. L. Immunological responses of L. donovani infection in mice and significance of T cell in resistance to experimental leishmaniasis. Clin Exp Immunol. 1980 Jun;40(3):508–514. [PMC free article] [PubMed] [Google Scholar]
  12. Zuckerman A. Current status of the immunology of blood and tissue Protozoa. I. Leishmania. Exp Parasitol. 1975 Dec;38(3):370–400. doi: 10.1016/0014-4894(75)90123-x. [DOI] [PubMed] [Google Scholar]

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