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Evaluation of immune responses raised against Tc13 antigens of Trypanosoma cruzi in the outcome of murine experimental infection

Published online by Cambridge University Press:  09 November 2007

G. A. GARCÍA ,
M. R. ARNAIZ ,
M. I. ESTEVA ,
S. A. LAUCELLA ,
P. A. GARAVAGLIA ,
S. E. IBARRA  and
A. M. RUIZ
G. A. GARCÍA*
Affiliation:
Instituto Nacional de Parasitología “Dr. Mario Fatala Chaben” – ANLIS/Malbrán, Paseo Colón 568 (cp: 1063), Buenos Aires, Argentina
M. R. ARNAIZ
Affiliation:
Instituto Nacional de Parasitología “Dr. Mario Fatala Chaben” – ANLIS/Malbrán, Paseo Colón 568 (cp: 1063), Buenos Aires, Argentina
M. I. ESTEVA
Affiliation:
Instituto Nacional de Parasitología “Dr. Mario Fatala Chaben” – ANLIS/Malbrán, Paseo Colón 568 (cp: 1063), Buenos Aires, Argentina
S. A. LAUCELLA
Affiliation:
Instituto Nacional de Parasitología “Dr. Mario Fatala Chaben” – ANLIS/Malbrán, Paseo Colón 568 (cp: 1063), Buenos Aires, Argentina
P. A. GARAVAGLIA
Affiliation:
Instituto Nacional de Parasitología “Dr. Mario Fatala Chaben” – ANLIS/Malbrán, Paseo Colón 568 (cp: 1063), Buenos Aires, Argentina
S. E. IBARRA
Affiliation:
Instituto Nacional de Parasitología “Dr. Mario Fatala Chaben” – ANLIS/Malbrán, Paseo Colón 568 (cp: 1063), Buenos Aires, Argentina
A. M. RUIZ
Affiliation:
Instituto Nacional de Parasitología “Dr. Mario Fatala Chaben” – ANLIS/Malbrán, Paseo Colón 568 (cp: 1063), Buenos Aires, Argentina
*
*Corresponding author. Tel: +54 11 4331 2330. Fax: +54 11 4331 7142. E-mail: gaandgarcia@yahoo.com
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Summary

We have previously reported that genetic immunization with Tc13Tul antigen of Trypanosoma cruzi, the aetiological agent of Chagas' disease, triggers harmful effects and non-protective immune responses. In order to confirm the role of Tc13 antigens during T. cruzi infection, herein we studied the humoral and cellular immune responses to the Tc13Tul molecule and its EPKSA C-terminal portion in BALB/c T. cruzi-infected mice or mice immunized with recombinant Tc13Tul. Analysis of the antibody response showed that B-cell epitopes that stimulate a sustained IgM production along the infection and high levels of IgG in the acute phase are mainly located at the Tc13 N- and C-terminal domains, respectively. DTH assays showed that T-cell epitopes are mainly at the Tc13 N-terminal segment and that they do not elicit an efficient memory response. Recombinant Tc13Tul did not induce IFN-γ secretion in either infected or immunized mice. However, a putative CD8+Tc13Tul-derived peptide was found to elicit IFN-γ production in chronically infected animals. Immunization with recombinant Tc13Tul did not induce pathology in tissues and neither did it protect against the infection. Our results show that in the outcome of T. cruzi infection the Tc13 family protein mainly triggers non-protective immune responses.

Keywords

Chagas' diseasetrans-sialidaseimmunizationpathology
Type
Original Articles
Information
Parasitology , Volume 135 , Issue 3 , March 2008 , pp. 347 - 357
Copyright
Copyright © Cambridge University Press 2007

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References

REFERENCES

Ben Younes-Chennoufi, A., Said, G., Eisen, H., Durand, A. and Hontebeyrie-Joskowicz, M. (1988). Cellular immunity to Trypanosoma cruzi is mediated by helper T cells (CD4+). Transactions of the Royal Society of Tropical Medicine and Hygiene 82, 84–89.CrossRefGoogle ScholarPubMed
Black, C. A. (1999). Delayed type hypersensitivity: current theories with an historic perspective. Dermatology Online Journal 5, 7.Google Scholar
Boscardin, S. B., Kinoshita, S. S., Fujimura, A. E. and Rodrigues, M. M. (2003). Immunization with cDNA expressed by amastigotes of Trypanosoma cruzi elicits protective immune response against experimental infection. Infection and Immunity 71, 2744–2757.CrossRefGoogle ScholarPubMed
Burns, J. M. Jr., Shreffler, W. G., Rosman, D. E., Sleath, P. R., March, C. J. and Reed, S. G. (1992). Identification and synthesis of a major conserved antigenic epitope of Trypanosoma cruzi. Proceedings of the National Academy of Sciences, USA 89, 1239–1243.Google Scholar
Bustamante, J. M., Rivarola, H. W., Fernandez, A. R., Enders, J. E., Ricardo, F., d'Oro Gloria, D. L., Palma, J. A. and Paglini-Oliva, P. A. (2003). Trypanosoma cruzi reinfections provoke synergistic effect and cardiac beta-adrenergic receptors' dysfunction in the acute phase of experimental Chagas' disease. Experimental Parasitology 103, 136–142.Google Scholar
Campetella, O., Sanchez, D., Cazzulo, J. J. and Frasch, A. C. (1992). A superfamily of Trypanosoma cruzi surface antigens. Parasitology Today 8, 378–381.CrossRefGoogle ScholarPubMed
Cross, G. A. and Takle, G. B. (1993). The surface trans-sialidase family of Trypanosoma cruzi. Annual Reviews of Microbiology 47, 385–411.Google Scholar
El-Sayed, N. M., Myler, P. J., Bartholomeu, D. C., Nilsson, D., Aggarwal, G., Tran, A. N., Ghedin, E., Worthey, E. A., Delcher, A. L., Blandin, G., Westenberger, S. J., Caler, E., Cerqueira, G. C., Branche, C., Haas, B., Anupama, A., Arner, E., Aslund, L., Attipoe, P., Bontempi, E., Bringaud, F., Burton, P., Cadag, E., Campbell, D. A., Carrington, M., Crabtree, J., Darban, H., da Silveira, J. F., de Jong, P., Edwards, K., Englund, P. T., Fazelina, G., Feldblyum, T., Ferella, M., Frasch, A. C., Gull, K., Horn, D., Hou, L., Huang, Y., Kindlund, E., Klingbeil, M., Kluge, S., Koo, H., Lacerda, D., Levin, M. J., Lorenzi, H., Louie, T., Machado, C. R., McCulloch, R., McKenna, A., Mizuno, Y., Mottram, J. C., Nelson, S., Ochaya, S., Osoegawa, K., Pai, G., Parsons, M., Pentony, M., Pettersson, U., Pop, M., Ramirez, J. L., Rinta, J., Robertson, L., Salzberg, S. L., Sanchez, D. O., Seyler, A., Sharma, R., Shetty, J., Simpson, A. J., Sisk, E., Tammi, M. T., Tarleton, R., Teixeira, S., Van Aken, S., Vogt, C., Ward, P. N., Wickstead, B., Wortman, J., White, O., Fraser, C. M., Stuart, K. D. and Andersson, B. (2005). The genome sequence of Trypanosoma cruzi, etiologic agent of Chagas disease. Science 309, 409–415.Google Scholar
Frasch, A. C. (2000). Functional diversity in the trans-sialidase and mucin families in Trypanosoma cruzi. Parasitology Today 16, 282–286.CrossRefGoogle ScholarPubMed
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 ScholarPubMed
Garcia, G. A., Arnaiz, M. R., Laucella, S. A., Esteva, M. I., Ainciart, N., Riarte, A., Garavaglia, P. A., Fichera, L. E. and Ruiz, A. M. (2006). Immunological and pathological responses in BALB/c mice induced by genetic administration of Tc13Tul antigen of Trypanosoma cruzi. Parasitology 132, 855–866.CrossRefGoogle Scholar
Garcia, G. A., Joensen, L. G., Bua, J., Ainciart, N, Perry, S. J. and Ruiz, A. M. (2003). Trypanosoma cruzi: molecular identification and characterization of new members of the Tc13 family. Description of the interaction between the Tc13 antigen from Tulahuen strain and the second extracellular loop of the beta(1)-adrenergic receptor. Experimental Parasitology 103, 112–119.CrossRefGoogle ScholarPubMed
Gomez-Garcia, L., Alejandre-Aguilar, R., Aranda-Fraustro, A., Lopez, R. and Monteon, V. M. (2005). Description of inflammation and cytokine profile at the inoculation site and in heart tissue of mice re-infected with Trypanosoma cruzi vector derived-metacyclic trypomastigotes. Parasitology 130, 511–522.CrossRefGoogle Scholar
Gorelik, G., Cremaschi, G., Borda, E. and Sterin-Borda, L. (1998). Trypanosoma cruzi antigens down-regulate T lymphocyte proliferation by muscarinic cholinergic receptor-dependent release of PGE2. Acta Physiologica, Pharmacologica et Therapeutica Latinoamericana 48, 115–123.Google Scholar
Ibanez, C. F., Affranchino, J. L. and Frasch, A. C. (1987). Antigenic determinants of Trypanosoma cruzi defined by cloning of parasite DNA. Molecular and Biochemical Parasitology 25, 175–184.CrossRefGoogle ScholarPubMed
Joensen, L., Borda, E., Kohout, T., Perry, S., Garcia, G. and Sterin-Borda, L. (2003). Trypanosoma cruzi antigen that interacts with the beta1-adrenergic receptor and modifies myocardial contractile activity. Molecular and Biochemical Parasitology 127, 169–177.Google Scholar
Martin, D. and Tarleton, R. (2004). Generation, specificity, and function of CD8+T cells in Trypanosoma cruzi infection. Immunological Reviews 201, 304–317.Google Scholar
Martin, D. L., Weatherly, D. B., Laucella, S. A., Cabinian, M. A., Crim, M. T., Sullivan, S., Heiges, M., Craven, S. H., Rosenberg, C. S., Collins, M. H., Sette, A., Postan, M. and Tarleton, R. L. (2006). CD8+T-cell responses to Trypanosoma cruzi are highly focused on strain-variant trans-sialidase epitopes. PLoS Pathogens 2, e77.CrossRefGoogle ScholarPubMed
Millar, A. E., Wleklinski-Lee, M. and Kahn, S. J. (1999). The surface protein superfamily of Trypanosoma cruzi stimulates a polarized Th1 response that becomes anergic. The Journal of Immunology 162, 6092–6099.CrossRefGoogle ScholarPubMed
Mucci, J., Risso, M. G., Leguizamon, M. S., Frasch, A. C. and Campetella, O. (2006). The trans-sialidase from Trypanosoma cruzi triggers apoptosis by target cell sialylation. Cellular Microbiology 8, 1086–1095.CrossRefGoogle ScholarPubMed
Peralta, J. M., Teixeira, M. G., Shreffler, W. G., Pereira, J. B., Burns, J. M. Jr., Sleath, P. R. and Reed, S. G. (1994). Serodiagnosis of Chagas' disease by enzyme-linked immunosorbent assay using two synthetic peptides as antigens. Journal of Clinical Microbiology 32, 971–974.Google Scholar
Reis, M. M., Higuchi Mde, L., Benvenuti, L. A., Aiello, V. D., Gutierrez, P. S., Bellotti, G. and Pileggi, F. (1997). An in situ quantitative immunohistochemical study of cytokines and IL-2R+in chronic human chagasic myocarditis: correlation with the presence of myocardial Trypanosoma cruzi antigens. Clinical Immunology and Immunopathology 83, 165–172.Google Scholar
Rodrigues, M. M., Ribeirao, M., Pereira-Chioccola, V., Renia, L. and Costa, F. (1999). Predominance of CD4 Th1 and CD8 Tc1 cells revealed by characterization of the cellular immune response generated by immunization with a DNA vaccine containing a Trypanosoma cruzi gene. Infection and Immunity 67, 3855–3863.Google Scholar
Sun, J. and Tarleton, R. L. (1993). Predominance of CD8+T lymphocytes in the inflammatory lesions of mice with acute Trypanosoma cruzi infection. American Journal of Tropical Medicine and Hygiene 48, 161–169.Google 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.Google Scholar
Whitton, J. L., Rodriguez, F., Zhang, J. and Hassett, D. E. (1999). DNA immunization: mechanistic studies. Vaccine 17, 1612–1619.CrossRefGoogle ScholarPubMed
World Health Organization. (2002). Control of Chagas disease. WHO Technical Report Series 905, 1–109.Google Scholar
Wizel, B., Nunes, M. and Tarleton, R. L. (1997). Identification of Trypanosoma cruzi trans-sialidase family members as targets of protective CD8+TC1 responses. The Journal of Immunology 159, 6120–6130.Google Scholar
Wrightsman, R. A., Dawson, B. D., Fouts, D. L. and Manning, J. E. (1994). Identification of immunodominant epitopes in Trypanosoma cruzi trypomastigote surface antigen-1 protein that mask protective epitopes. The Journal of Immunology 153, 3148–3154.CrossRefGoogle ScholarPubMed