Skip to main content
PMC home page
Infection and Immunity logoLink to Infection and Immunity
. 1997 Jul;65(7):2548–2554. doi: 10.1128/iai.65.7.2548-2554.1997

Passive transfer of a monoclonal antibody specific for a sialic acid-dependent epitope on the surface of Trypanosoma cruzi trypomastigotes reduces infection in mice.

G Franchin 1, V L Pereira-Chioccola 1, S Schenkman 1, M M Rodrigues 1
PMCID: PMC175360  PMID: 9199418

Abstract

Trypanosoma cruzi, the parasite that causes Chagas' disease, proliferates in the cytosol of mammalian cells. When the trypomastigote forms exit the infected cell, they become extensively sialylated because the parasite contains an enzyme called trans-sialidase. This enzyme efficiently catalyzes the transfer of bound sialic acid residues from host glycoconjugates to acceptors containing terminal beta-galactosyl residues on the parasite surface. The sialic acid acceptors are developmentally regulated mucin-like glycoproteins that are extremely abundant on the trypomastigote surface. In the present study, we determined whether passive transfer of monoclonal antibodies specific for sialic acid acceptors could reduce the acute infection induced by T. cruzi in a highly susceptible mouse strain. We found that passive transfer to naive mice of an immunoglobulin G1 monoclonal antibody directed to a sialylated epitope of these mucin-like glycoproteins significantly decreased parasitemia and the number of tissue parasites as measured by a DNA probe specific for T. cruzi. Upon challenge with trypomastigotes, mice which received this antibody also had a significant increase in survival. A statistically significant reduction in parasitemia could be accomplished with relatively small doses of immunoglobulin, and Fab fragments alone could not mediate protective immunity. The precise mechanism of parasite elimination is unknown; however, this monoclonal antibody does not lyse trypomastigotes in vitro in the presence of human complement or mouse spleen cells.

Full Text

The Full Text of this article is available as a PDF (196.5 KB).

Selected References

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

  1. Acosta A., Schenkman R. P., Schenkman S. Sialic acid acceptors of different stages of Trypanosoma cruzi are mucin-like glycoproteins linked to the parasite membrane by GPI anchors. Braz J Med Biol Res. 1994 Feb;27(2):439–442. [PubMed] [Google Scholar]
  2. Almeida I. C., Ferguson M. A., Schenkman S., Travassos L. R. Lytic anti-alpha-galactosyl antibodies from patients with chronic Chagas' disease recognize novel O-linked oligosaccharides on mucin-like glycosyl-phosphatidylinositol-anchored glycoproteins of Trypanosoma cruzi. Biochem J. 1994 Dec 15;304(Pt 3):793–802. doi: 10.1042/bj3040793. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Almeida I. C., Milani S. R., Gorin P. A., Travassos L. R. Complement-mediated lysis of Trypanosoma cruzi trypomastigotes by human anti-alpha-galactosyl antibodies. J Immunol. 1991 Apr 1;146(7):2394–2400. [PubMed] [Google Scholar]
  4. Andrews N. W., Hong K. S., Robbins E. S., Nussenzweig V. Stage-specific surface antigens expressed during the morphogenesis of vertebrate forms of Trypanosoma cruzi. Exp Parasitol. 1987 Dec;64(3):474–484. doi: 10.1016/0014-4894(87)90062-2. [DOI] [PubMed] [Google Scholar]
  5. Chuenkova M., Pereira M. E. Trypanosoma cruzi trans-sialidase: enhancement of virulence in a murine model of Chagas' disease. J Exp Med. 1995 May 1;181(5):1693–1703. doi: 10.1084/jem.181.5.1693. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Ciavaglia M. do C., de Carvalho T. U., de Souza W. Interaction of Trypanosoma cruzi with cells with altered glycosylation patterns. Biochem Biophys Res Commun. 1993 Jun 15;193(2):718–721. doi: 10.1006/bbrc.1993.1684. [DOI] [PubMed] [Google Scholar]
  7. Colli W. Trans-sialidase: a unique enzyme activity discovered in the protozoan Trypanosoma cruzi. FASEB J. 1993 Oct;7(13):1257–1264. doi: 10.1096/fasebj.7.13.8405811. [DOI] [PubMed] [Google Scholar]
  8. Cross G. A., Takle G. B. The surface trans-sialidase family of Trypanosoma cruzi. Annu Rev Microbiol. 1993;47:385–411. doi: 10.1146/annurev.mi.47.100193.002125. [DOI] [PubMed] [Google Scholar]
  9. Gonzalez A., Prediger E., Huecas M. E., Nogueira N., Lizardi P. M. Minichromosomal repetitive DNA in Trypanosoma cruzi: its use in a high-sensitivity parasite detection assay. Proc Natl Acad Sci U S A. 1984 Jun;81(11):3356–3360. doi: 10.1073/pnas.81.11.3356. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. KAGAN I. G., NORMAN L. Immunologic studies on Trypanosoma cruzi. III. Duration of acquired immunity in mice initially infected with a North American strain of T. cruzi. J Infect Dis. 1961 Mar-Apr;108:213–217. doi: 10.1093/infdis/108.2.213. [DOI] [PubMed] [Google Scholar]
  11. Klein-Schneegans A. S., Kuntz L., Trembleau S., Fonteneau P., Loor F. Serum concentrations of IgM, IgG1, IgG2b, IgG3 and IgA in C57BL/6 mice and their congenics at the nu(nude)locus. Thymus. 1990 Aug;16(1):45–54. [PubMed] [Google Scholar]
  12. Krettli A. U., Brener Z. Protective effects of specific antibodies in Trypanosoma cruzi infections. J Immunol. 1976 Mar;116(3):755–760. [PubMed] [Google Scholar]
  13. Krettli A. U., Weisz-Carrington P., Nussenzweig R. S. Membrane-bound antibodies to bloodstream Trypanosoma cruzi in mice: strain differences in susceptibility to complement-mediated lysis. Clin Exp Immunol. 1979 Sep;37(3):416–423. [PMC free article] [PubMed] [Google Scholar]
  14. Lima-Martins M. V., Sanchez G. A., Krettli A. U., Brener Z. Antibody-dependent cell cytotoxicity against Trypanosoma cruzi is only mediated by protective antibodies. Parasite Immunol. 1985 Jul;7(4):367–376. doi: 10.1111/j.1365-3024.1985.tb00083.x. [DOI] [PubMed] [Google Scholar]
  15. Ming M., Chuenkova M., Ortega-Barria E., Pereira M. E. Mediation of Trypanosoma cruzi invasion by sialic acid on the host cell and trans-sialidase on the trypanosome. Mol Biochem Parasitol. 1993 Jun;59(2):243–252. doi: 10.1016/0166-6851(93)90222-j. [DOI] [PubMed] [Google Scholar]
  16. Pereira M. E., Zhang K., Gong Y., Herrera E. M., Ming M. Invasive phenotype of Trypanosoma cruzi restricted to a population expressing trans-sialidase. Infect Immun. 1996 Sep;64(9):3884–3892. doi: 10.1128/iai.64.9.3884-3892.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Ravetch J. V., Kinet J. P. Fc receptors. Annu Rev Immunol. 1991;9:457–492. doi: 10.1146/annurev.iy.09.040191.002325. [DOI] [PubMed] [Google Scholar]
  18. Schenkman R. P., Vandekerckhove F., Schenkman S. Mammalian cell sialic acid enhances invasion by Trypanosoma cruzi. Infect Immun. 1993 Mar;61(3):898–902. doi: 10.1128/iai.61.3.898-902.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Schenkman S., Andrews N. W., Nussenzweig V., Robbins E. S. Trypanosoma cruzi invade a mammalian epithelial cell in a polarized manner. Cell. 1988 Oct 7;55(1):157–165. doi: 10.1016/0092-8674(88)90018-9. [DOI] [PubMed] [Google Scholar]
  20. Schenkman S., Diaz C., Nussenzweig V. Attachment of Trypanosoma cruzi trypomastigotes to receptors at restricted cell surface domains. Exp Parasitol. 1991 Jan;72(1):76–86. doi: 10.1016/0014-4894(91)90123-e. [DOI] [PubMed] [Google Scholar]
  21. Schenkman S., Eichinger D., Pereira M. E., Nussenzweig V. Structural and functional properties of Trypanosoma trans-sialidase. Annu Rev Microbiol. 1994;48:499–523. doi: 10.1146/annurev.mi.48.100194.002435. [DOI] [PubMed] [Google Scholar]
  22. Schenkman S., Jiang M. S., Hart G. W., Nussenzweig V. A novel cell surface trans-sialidase of Trypanosoma cruzi generates a stage-specific epitope required for invasion of mammalian cells. Cell. 1991 Jun 28;65(7):1117–1125. doi: 10.1016/0092-8674(91)90008-m. [DOI] [PubMed] [Google Scholar]
  23. Schenkman S., Kurosaki T., Ravetch J. V., Nussenzweig V. Evidence for the participation of the Ssp-3 antigen in the invasion of nonphagocytic mammalian cells by Trypanosoma cruzi. J Exp Med. 1992 Jun 1;175(6):1635–1641. doi: 10.1084/jem.175.6.1635. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Schenkman S., Pontes de Carvalho L., Nussenzweig V. Trypanosoma cruzi trans-sialidase and neuraminidase activities can be mediated by the same enzymes. J Exp Med. 1992 Feb 1;175(2):567–575. doi: 10.1084/jem.175.2.567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Umekita L. F., Takehara H. A., Mota I. Role of the antibody Fc in the immune clearance of Trypanosoma cruzi. Immunol Lett. 1988 Jan;17(1):85–89. doi: 10.1016/0165-2478(88)90106-x. [DOI] [PubMed] [Google Scholar]

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

RESOURCES