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Immune system pathogenesis is prevented by the neutralization of the systemic trans-sialidase from Trypanosoma cruzi during severe infections

Published online by Cambridge University Press:  14 December 2006

M. G. RISSO ,
T. A. PITCOVSKY ,
R. L. CACCURI ,
O. CAMPETELLA  and
M. S. LEGUIZAMÓN
M. G. RISSO
Affiliation:
Departamento de Microbiología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina
T. A. PITCOVSKY
Affiliation:
Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín, Buenos Aires, Argentina
R. L. CACCURI
Affiliation:
Departamento de Microbiología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina
O. CAMPETELLA
Affiliation:
Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín, Buenos Aires, Argentina
M. S. LEGUIZAMÓN
Affiliation:
Departamento de Microbiología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina
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Abstract

During the acute phase of Trypanosoma cruzi infection, strong haematological and immune system alterations are observed. The parasite expresses trans-sialidase, a virulence factor responsible for the sialylation of its surface glycoconjugates. This enzyme is also shed to the bloodstream where it is associated with immune system alterations triggered during the infection. During experimental and human infections, the host elicits antibodies able to neutralize the enzyme activity that would be responsible for restricting systemic trans-sialidase to the early steps of the infection, when major immune alterations are induced. The actual relevance of these antibodies was tested by passive transference of monoclonal neutralizing antibodies in acute infection models displaying extreme sensitivity to the infection. Mice were inoculated with virulent parasite strains that induce high parasitaemia, early mortality and strong immune tissue abnormalities. The trans-sialidase-neutralizing antibodies were able to preserve B cell areas both in ganglia and spleen as well as the thymus architecture even in these extreme models. Although no differences between control and treated mice regarding animal survival were found, a major role for the humoral response in controlling the damage of the immune system induced by a systemically distributed virulence factor was defined in an infection with a eukaryotic pathogen.

Keywords

apoptosisChagas diseaseneutralizing antibodiestrans-sialidaseTrypanosoma cruzivirulence factors
Type
Research Article
Information
Parasitology , Volume 134 , Issue 4 , April 2007 , pp. 503 - 510
Copyright
© 2006 Cambridge University Press

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References

REFERENCES

Acosta-Serrano, A., Almeida, I. C., Freitas-Junior, L. H., Yoshida, N. and Schenkman, S. ( 2001). The mucin-like glycoprotein super-family of Trypanosoma cruzi: structure and biological roles. Molecular and Biochemical Parasitology 114, 143–150.CrossRefGoogle Scholar
Alvarez, P., Buscaglia, C. A. and Campetella, O. ( 2004). Improving protein pharmacokinetics by genetic fusion to simple amino acid sequences. The Journal of Biological Chemistry 279, 3375–3381.CrossRefGoogle Scholar
Alvarez, P., Leguizamón, M. S., Buscaglia, C. A., Pitcovsky, T. A. and Campetella, O. ( 2001). Multiple overlapping epitopes in the repetitive unit of the shed acute-phase antigen from Trypanosoma cruzi enhance its immunogenic properties. Infection and Immunity 69, 7946–7949.CrossRefGoogle Scholar
Buscaglia, C. A., Alfonso, J., Campetella, O. and Frasch, A. C. ( 1999). Tandem amino acid repeats from Trypanosoma cruzi shed antigens increase the half-life of proteins in blood. Blood 93, 2025–2032.Google Scholar
Chuenkova, M. and Pereira, M. E. ( 1995). Trypanosoma cruzi trans-sialidase: enhancement of virulence in a murine model of Chagas' disease. Journal of Experimental Medicine 181, 1693–1703.CrossRefGoogle Scholar
Costa, F., Franchin, G., Pereira-Chioccola, V. L., Ribeirao, M., Schenkman, S. and Rodrigues, M. M. ( 1998). Immunization with a plasmid DNA containing the gene of trans-sialidase reduces Trypanosoma cruzi infection in mice. Vaccine 16, 768–774.CrossRefGoogle Scholar
Cummings, M. C., Winterfod, C. M. and Walker, N. I. ( 1997). Apoptosis. In Histology for Pathologists ( ed. Sternberg, S. F.), pp. 3–21. Lippincot-Raven Publishers, Philadelphia.CrossRef
Fralish, B. H. and Tarleton, R. L. ( 2003). Genetic immunization with LYT1 or a pool of trans-sialidase genes protects mice from lethal Trypanosoma cruzi infection. Vaccine 21, 3070–3080.CrossRefGoogle Scholar
Franchin, G., Pereira-Chioccola, V. L., Schenkman, S. and Rodrigues, M. M. ( 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. Infection and Immunity 65, 2548–2554.Google Scholar
Frasch, A. C. ( 2000). Functional diversity in the trans-sialidase and mucin families in Trypanosoma cruzi. Parasitology Today 16, 282–286.CrossRefGoogle Scholar
Fujimura, A. E., Kinoshita, S. S., Pereira-Chioccola, V. L. and Rodrigues, M. M. ( 2001). DNA sequences encoding CD4+ and CD8+ T-cell epitopes are important for efficient protective immunity induced by DNA vaccination with a Trypanosoma cruzi gene. Infection and Immunity 69, 5477–5486.CrossRefGoogle Scholar
Garg, N. and Tarleton, R. L. ( 2002). Genetic immunization elicits antigen-specific protective immune responses and decreases disease severity in Trypanosoma cruzi infection. Infection and Immunity 70, 5547–5555.CrossRefGoogle Scholar
Hall, B. F., Webster, P., Ma, A. K., Joiner, K. A. and Andrews, N. W. ( 1992). Desialylation of lysosomal membrane glycoproteins by Trypanosoma cruzi: a role for the surface neuraminidase in facilitating parasite entry into the host cell cytoplasm. Journal of Experimental Medicine 176, 313–325.CrossRefGoogle Scholar
Harmon, B. V., Winterford, C. M., O'Brien, B. A. and Allan, D. J. ( 1998). Morphological criteria for identifying apoptosis. In Cell Biology: A Laboratory Handbook, Vol. 1 ( ed. Celis, J.), pp. 327–340. Academic Press, San Diego, CA, USA.
Katae, M., Miyahira, Y., Takeda, K., Matsuda, H., Yagita, H., Okumura, K., Takeuchi, T., Kamiyama, T., Ohwada, A., Fukuchi, Y. and Aoki, T. ( 2002). Coadministration of an interleukin-12 gene and a Trypanosoma cruzi gene improves vaccine efficacy. Infection and Immunity 70, 4833–4840.CrossRefGoogle Scholar
Leguizamón, M. S., Campetella, O. E., González Cappa, S. M. and Frasch, A. C. ( 1994). Mice infected with Trypanosoma cruzi produce antibodies against the enzymatic domain of trans-sialidase that inhibit its activity. Infection and Immunity 62, 3441–3446.Google Scholar
Leguizamón, M. S., Mocetti, E., Garcia Rivello, H., Argibay, P. and Campetella, O. ( 1999). Trans-sialidase from Trypanosoma cruzi induces apoptosis in cells from the immune system in vivo. Journal of Infectious Diseases 180, 1398–1402.CrossRefGoogle Scholar
Leguizamón, M. S., Russomando, G., Luquetti, A., Rassi, A., Almiron, M., González-Cappa, S. M., Frasch, A. C. and Campetella, O. ( 1997). Long-lasting antibodies detected by a trans-sialidase inhibition assay of sera from parasite-free, serologically cured chagasic patients. Journal of Infectious Diseases 175, 1272–1275.CrossRefGoogle Scholar
Minoprio, P. ( 2003). Impact of polyclonal lymphocyte responses on parasite evasion and persistence. In Molecular Mechanisms of Pathogenesis in Chagas Disease ( ed. Kelly, J. M.), pp. 101–110. Kluver Academic/Plenum Publisher, New York.
Mucci, J., Hidalgo, A., Mocetti, E., Argibay, P. F., Leguizamón, M. S. and Campetella, O. ( 2002). Thymocyte depletion in Trypanosoma cruzi infection is mediated by trans-sialidase-induced apoptosis on nurse cells complex. Proceedings of the National Academy of Sciences, USA 99, 3896–3901.CrossRefGoogle Scholar
Mucci, J., Risso, M. G., Leguizamón, M. S., Frasch, A. C. C. and Campetella, O. ( 2006). The trans-sialidase from Trypanosoma cruzi triggers apoptosis by target cell sialylation. Cellular Microbiology 8, 1086–1095. doi: 10.1111/j.1462-5822.2006.00689.x.CrossRefGoogle Scholar
Mussalem, J. S., Vasconcelos, J. R. C., Squaiella, C. C., Zeigler Ananias, R., Goncalves Braga, E., Rodrigues, M. M. and Longo-Maugéri, I. M. ( 2006). Adjuvant effect of the Propionibacterium acnes and its purified soluble polysacharide on the immunization with plasmidial DNA containing a Trypanosoma cruzi gene. Microbiology and Immunology 50, 253–263.CrossRefGoogle Scholar
Pereira-Chioccola, V. L., Acosta-Serrano, A., Correia de Almeida, I., Ferguson, M. A., Souto-Padron, T., Rodrigues, M. M., Travassos, L. R. and Schenkman, S. ( 2000). Mucin-like molecules form a negatively charged coat that protects Trypanosoma cruzi trypomastigotes from killing by human anti-alpha-galactosyl antibodies. Journal of Cell Science 113, 1299–1307.Google Scholar
Pereira-Chioccola, V. L., Schenkman, S. and Kloetzel, J. K. ( 1994). Sera from chronic Chagasic patients and rodents infected with Trypanosoma cruzi inhibit trans-sialidase by recognizing its amino-terminal and catalytic domain. Infection and Immunity 62, 2973–2978.Google Scholar
Pitcovsky, T. A., Buscaglia, C. A., Mucci, J. and Campetella, O. ( 2002). A functional network of intramolecular cross-reacting epitopes delays the elicitation of neutralizing antibodies to Trypanosoma cruzi trans-sialidase. Journal of Infectious Diseases 186, 397–404.CrossRefGoogle Scholar
Pitcovsky, T. A., Mucci, J., Alvarez, P., Leguizamón, M. S., Burrone, O., Alzari, P. M. and Campetella, O. ( 2001). Epitope mapping of trans-sialidase from Trypanosoma cruzi reveals the presence of several cross-reactive determinants. Infection and Immunity 69, 1869–1875.CrossRefGoogle Scholar
Risso, M. G., Garbarino, G. B., Mocetti, E., Campetella, O., González Cappa, S. M., Buscaglia, C. A. and Leguizamón, M. S. ( 2004). Differential expression of a virulence factor, the trans-sialidase, by the main Trypanosoma cruzi phylogenetic lineages. Journal of Infectious Diseases 189, 2250–2259.CrossRefGoogle Scholar
Rubin-de-Celis, S. S., Uemura, H., Yoshida, N. and Schenkman, S. ( 2006). Expression of trypomastigote trans-sialidase in metacyclic forms of Trypanosoma cruzi increases parasite escape from its parasitophorous vacuole. Cellular Microbiology doi:10.1111/j.1462-5822.2006.00755.x (in the Press).CrossRefGoogle Scholar
Savino, W., Leite-de-Moraes, M. C., Hontebeyrie-Joskowicz, M. and Dardenne, M. ( 1989). Studies on the thymus in Chagas' disease. I. Changes in the thymic microenvironment in mice acutely infected with Trypanosoma cruzi. European Journal of Immunology 19, 1727–1733.CrossRefGoogle Scholar
Schenkman, S., Kurosaki, T., Ravetch, J. V. and Nussenzweig, V. ( 1992). Evidence for the participation of the Ssp-3 antigen in the invasion of nonphagocytic mammalian cells by Trypanosoma cruzi. Journal of Experimental Medicine 175, 1635–1641.CrossRefGoogle Scholar
Taliaferro, W. H. and Pizzi, T. ( 1955). Connective tissue reactions in normal and immunized mice to a reticulotropic strain of Trypanosoma cruzi. Journal of Infectious Diseases 96, 199–226.CrossRefGoogle Scholar
Tomlinson, S., Pontes de Carvalho, L. C., Vandekerckhove, F. and Nussenzweig, V. ( 1994). Role of sialic acid in the resistance of Trypanosoma cruzi trypomastigotes to complement. Journal of Immunology 153, 3141–3147.Google Scholar
Tribulatti, M. V., Mucci, J., Van Rooijen, N., Leguizamón, M. S. and Campetella, O. ( 2005). The trans-Sialidase from Trypanosoma cruzi induces thrombocytopenia during acute Chagas' disease by reducing the platelet sialic acid contents. Infection and Immunity 73, 201–207.CrossRefGoogle Scholar
Vasconcelos, J. R., Hiyane, M. I., Marinho, C. R., Claser, C., Machado, A. M., Gazzinelli, R. T., Bruna-Romero, O., Alvarez, J. M., Boscardin, S. B. and Rodrigues, M. M. ( 2004). Protective immunity against Trypanosoma cruzi infection in a highly susceptible mouse strain after vaccination with genes encoding the amastigote surface protein-2 and trans-sialidase. Human Gene Therapy 15, 878–886.CrossRefGoogle Scholar
Villalta, F., Smith, C. M., Burns, J. M., Jr., Chaudhuri, G. and Lima, M. F. ( 1996). Fab' fragments of a mAb to a member of family 2 of trans-sialidases of Trypanosoma cruzi block trypanosome invasion of host cells and neutralize infection by passive immunization. Annals of the New York Academy of Sciences 797, 242–245.CrossRefGoogle Scholar
Yoshida, N. ( 2003). Trypanosoma cruzi cell invasion mechanisms. In American Trypanosomiasis, Vol. 7 ( ed. Tyler, K. M. and Miles, M. A.), pp. 69–79. Kluwer Academic Publishers, New York.CrossRef
Zúñiga, E., Motran, C., Montes, C. L., Diaz, F. L., Bocco, J. L. and Gruppi, A. ( 2000). Trypanosoma cruzi-induced immunosuppression: B cells undergo spontaneous apoptosis and lipopolysaccharide (LPS) arrests their proliferation during acute infection. Clinical and Experimental Immunology 119, 507–515.CrossRefGoogle Scholar