Hostname: page-component-78c5997874-fbnjt Total loading time: 0 Render date: 2024-11-11T07:01:18.209Z Has data issue: false hasContentIssue false

Comparative study of the presence of Trypanosoma cruzi kDNA, inflammation and denervation in chagasic patients with and without megaesophagus

Published online by Cambridge University Press:  04 July 2005

A. B. M. da SILVEIRA
Affiliation:
Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Pampulha, CEP: 31270-901, Belo Horizonte, Minas Gerais,Brazil
R. M. E. ARANTES
Affiliation:
Department of General Pathology, ICB, UFMG, Belo Horizonte, Minas Gerais, Brazil
A. R. VAGO
Affiliation:
Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Pampulha, CEP: 31270-901, Belo Horizonte, Minas Gerais,Brazil
E. M. LEMOS
Affiliation:
Department of Pathology, UFES, Vitória, Espírito Santo, Brazil
S. J. ADAD
Affiliation:
Department of Pathology, Medical School of Triângulo Mineiro, Uberaba, Minas Gerais, Brazil
R. CORREA-OLIVEIRA
Affiliation:
Centro de Pesquisas René Rachou, FIOCRUZ, Belo Horizonte, Minas Gerais, Brazil
D. D'AVILA REIS
Affiliation:
Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Pampulha, CEP: 31270-901, Belo Horizonte, Minas Gerais,Brazil

Abstract

Neuronal lesions have been considered the hallmark of chagasic megaesophagus, but the role of Trypanosoma cruzi and the participation of the inflammatory cells in this process are still debated. In the present study we counted neurons in the oesophagus from patients with and without megaesophagus and further examined these samples for the presence of parasite kDNA and cells with cytolytic potential (Natural Killer cells, cytotoxic lymphocytes and macrophages). The presence of parasite kDNA was demonstrated in 100% of cases with megaesophagus and in 60% of patients without megaesophagus. When analysed for the number of neurons, the patients without megaesophagus could be classified into 2 groups, as having normal or a decreased number of neurons. The former group did not show any inflammatory process, but interestingly, all patients without megaesophagus presenting decreased number of neurons also presented both parasite kDNA and inflammatory process in the organ. We further observed that the numbers of cytotoxic cells in the myenteric plexus region inversely correlate with the number of neurons. These data together strongly suggest that chronic lesions in chagasic megaesophagus might be a consequence of immune-mediated mechanisms, that last until the chronic phase of infection, and are dependent on the persistence of parasite in the host's tissue.

Type
Research Article
Copyright
© 2005 Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Adad, S. J., Andrade, D. C., Lopes, E. R. and Chapadeiro, E. ( 1991). Contribuição ao estudo da anatomia patológica do megaesôfago chagásico. Revista do Instituto de Medicina Tropical de São Paulo 33, 443450.CrossRefGoogle Scholar
Benavides, G. R., Hubby, B., Grosse, W. M., McGraw, R. A. and Tarleton, R. L. ( 1995). Construction and use of a multi-competitor gene for quantitative RT-PCR using existing primer sets. Journal of Immunological Methods 181, 145156.CrossRefGoogle Scholar
Chapadeiro, E. ( 1999). Clinical evolution and morbi-mortality in Chagas disease. Memórias do Instituto Oswaldo Cruz 94, 309310.CrossRefGoogle Scholar
Corbett, C. E., Ribeiro, U. Jr., Prianti, M. G., Habr-Gama, A., Okumura, M. and Gama-Rodrigues, J. ( 2001). Cell-mediated immune response in megacolon from patients with chronic Chagas' disease. Diseases of the Colon and Rectum 44, 993998.CrossRefGoogle Scholar
Cossio, P. M., Diez, C., Szarfman, A., Kreutzer, E., Candiolo, B. and Arana, R. M. ( 1974). Chagasic cardiopathy. Demonstration of a serum gammaglobulin factor which reacts with endocardium and vascular structures. Circulation 49, 1321.Google Scholar
d'Avila Reis, D., Lemos, E. M., Silva, G. C., Adad, S. J., McCurley, T., Correa-Oliveira, R. and Machado, C. R. ( 2001). Phenotypic characterization of the inflammatory cells in chagasic megaesophagus. Transactions of the Royal Society of Tropical Medicine and Hygiene 95, 177178.CrossRefGoogle Scholar
de Oliveira, R. B., Troncon, L. E., Dantas, R. O. and Menghelli, U. G. ( 1998). Gastrointestinal manifestations of Chagas' disease. American Journal of Gastroenterology 93, 884889.CrossRefGoogle Scholar
Fuenmayor, C., Higuchi, M. L., Carrasco, H., Parada, H., Gutierrez, P., Aiello, V. and Palomino, S. ( 2005). Acute Chagas' disease: immunohistochemical characteristics of T cell infiltrate and its relationship with Trypanosoma cruzi parasitic antigens. Acta Cardiologica 60, 3337.CrossRefGoogle Scholar
Gomes, M. L., Macedo, A. M., Vago, A. R., Pena, S. D. J., Galvão, L. M. C. and Chiari, E. ( 1998). Trypanosoma cruzi: Optimization of Polymerase Chain Reaction for detection in human blood. Experimental Parasitology 88, 2833.CrossRefGoogle Scholar
Graefe, S. E. B., Jacobs, T., Gaworski, I., Klauenberg, U., Steeg, C. and Fleischer, B. ( 2003). Interleukin – 12 but not interleukin – 18 is required for immunity to Trypanosoma cruzi in mice. Microbes and Infection 5, 833839.CrossRefGoogle Scholar
Hoft, D. F. and Eickhoff, C. S. ( 2002). Type 1 immunity provides optimal protection against both mucosal and systemic Trypanosoma cruzi challenges. Infection and Immunity 70, 67156725.CrossRefGoogle Scholar
Kalil, J. and Cunha-Neto, E. ( 1996). Autoimmunity in Chagas disease cardiomiopathy: fulfilling the criteria at last? Parasitology Today 12, 396399.Google Scholar
Kerndt, P. R., Waskin, H. A., Kirchhoff, L. V., Steurer, F., Waterman, S. H., Nelson, J. M., Gellert, G. A. and Shulman, I. A. ( 1991). Prevalence of antibody to Trypanosoma cruzi among blood donors in Los Angeles, California. Transfusion 31, 814818.CrossRefGoogle Scholar
Kierszenbaum, F. ( 2003). Views on the autoimmunity hypothesis for Chagas disease pathogenesis. FEMS Immunology and Medical Microbiology 37, 111.CrossRefGoogle Scholar
Koberle, F. ( 1968). Chagas' disease and Chagas' syndromes. The pathology of american trypanosomiasis. Advances in Parasitology 6, 63116.Google Scholar
Lages-Silva, E., Crema, E., Ramirez, L. E., Macedo, A. M., Pena, S. D. and Chiari, E. ( 2001). Relationship between Trypanosoma cruzi and human chagasic megaesophagus: blood and tissue parasitism. The American Journal of Tropical Medicine and Hygiene 65, 435441.CrossRefGoogle Scholar
Levitus, G., Hontebeyrie-Joskowicz, M., Van Regenmortel, M. H. and Levin, M. J. ( 1991). Humoral autoimune response to ribosomal P proteins in chronic Chagas heart disease. Clinical and Experimental Immunology 85, 413417.Google Scholar
Mahler, E., Hoebeke, J. and Levin, M. J. ( 2004). Structural and functional complexity of the humoral response against the Trypanosoma cruzi ribosomal P2 beta protein in patients with chronic Chagas' heart disease. Clinical and Experimental Immunology 136, 527534.CrossRefGoogle Scholar
Melo, R. C. and Machado, C. R. ( 2001). Trypanosoma cruzi: peripheral blood monocytes and heart macrophages in the resistance to acute experimental infection in rats. Experimental Parasitology 97, 1523.CrossRefGoogle Scholar
Navin, T. R., Roberto, R. R., Juranek, D. D., Limpakarnjanarat, K., Mortenson, E. W., Clover, J. R., Yescott, R. E., Taclindo, C., Steurer, F. and Allain, D. ( 1985). Human and sylvatic Trypanosoma cruzi infection in California. American Journal of Public Health 75, 366369.CrossRefGoogle Scholar
Pontes-de-Carvalho, L., Santana, C. C., Soares, M. B., Oliveira, G. G., Cunha-Neto, E. and Ribeiro-dos-Santos, R. ( 2002). Experimental chronic Chagas' disease myocarditis is an autoimmune disease preventable by induction of immunological tolerance to myocardial antigens. Journal of Autoimmunity 18, 131138.CrossRefGoogle Scholar
Prata, A. ( 2001). Clinical and epidemiological aspects of Chagas disease. The Lancet Infectious Diseases 1, 92100.CrossRefGoogle Scholar
Reis, D. D., Jones, E. M., Tostes, S. Jr., Lopes, E. R., Gazzinelli, G., Colley, D. G. and McCurley, T. L. ( 1993). Characterization of inflammatory infiltrate in chronic chagasic myocardial lesions: presence of tumor necrosis factor cells and dominace of granzyme A, CD8+ lymphocytes. The American Journal of Tropical Medicine and Hygiene 48, 637644.CrossRefGoogle Scholar
Rezende, J. M. and Lauar, K. M. ( 1960). Aspectos clínicos e radiológicos da aperistálsis do esôfago. Revista Brasileira de Gastroenterologia 12, 247262.Google Scholar
Schijman, A. G., Altcheh, J., Burgos, J. M., Biancardi, M., Bisio, M., Levin, M. J. and Freilij, H. ( 2003). Aetiological treatment of congenital Chagas' disease diagnosed and monitored by the polymerase chain reaction. Journal of Antimicrobial Chemotherapy 52, 441449.CrossRefGoogle Scholar
Smith, L. A. and Wright-Kanuth, M. S. ( 2003). Transfusion-transmitted parasites. Clinical Laboratory Sciences 16, 239245.Google Scholar
Sturm, N. R., Degrave, W., Morel, C. and Simpson, L. ( 1989). Sensitive detection and schizodeme classification of Trypanosoma cruzi cells by amplification of kinetoplast minicircle DNA sequences: use in diagnosis of Chagas disease. Molecular and Biochemical Parasitology 33, 205214.CrossRefGoogle Scholar
Toledo, M. J., Bahia, M. T., Veloso, V. M., Carneiro, C. M., Machado-Coelho, G. L., Alves, C. F., Martins, H. R., Cruz, R. E., Tafuri, W. L. and Lana, M. ( 2004). Effects of specific treatment on parasitological and histopathological parameters in mice infected with different Trypanosoma cruzi clonal genotypes. Journal of Antimicrobial Chemotherapy 53, 10451053.CrossRefGoogle Scholar
Vago, A. R., Macedo, A. M., Adad, S. J., Reis, D. D. and Correa-Oliveira, R. ( 1996). PCR detection of Trypanosoma cruzi DNA in esophagus tissues of patients with chronic digestive Chagas' disease. Lancet 348, 891892.CrossRefGoogle Scholar
Vago, A. R., Silva, D. M., Adad, S. J., Correa-Oliveira, R. and d'Avila Reis, D. ( 2003). Chronic Chagas disease: presence of parasite DNA in esophagus without megaesophagus. Transactions of the Royal Society of Tropical Medicine and Hygiene 97, 308309.CrossRefGoogle Scholar