Staff View: Trypanosoma cruzi in the chicken model : Chagas-like heart disease in the absence of parasitism

Trypanosoma cruzi in the chicken model : Chagas-like heart disease in the absence of parasitism

Background: The administration of anti-trypanosome nitroderivatives curtails Trypanosoma cruzi infection in Chagas disease patients, but does not prevent destructive lesions in the heart. This observation suggests that an effective treatment for the disease requires understanding its pathogenesis. M...

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Main Authors:	Teixeira, Antonio Raimundo Lima Cruz, Gomes, Clever, Nitz, Nadjar, Sousa, Alessandro O., Alves, Rozeneide M., Guimaro, Maria C., Cordeiro, Ciro, Bernal, Francisco M., Rosa, Ana de Cássia, Hejnar, Jiri, Leonardecz, Eduardo, Hecht, Mariana M.
Format:	Artigo
Language:	Inglês
Published:	Plos 2019
Subjects:	Tripanossoma cruzi Chagas, Doença de Coração - doenças Galinha
Online Access:	http://repositorio.unb.br/handle/10482/33957
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spelling	ir-10482-339572019-02-06T15:38:25Z Trypanosoma cruzi in the chicken model : Chagas-like heart disease in the absence of parasitism Teixeira, Antonio Raimundo Lima Cruz Gomes, Clever Nitz, Nadjar Sousa, Alessandro O. Alves, Rozeneide M. Guimaro, Maria C. Cordeiro, Ciro Bernal, Francisco M. Rosa, Ana de Cássia Hejnar, Jiri Leonardecz, Eduardo Hecht, Mariana M. Tripanossoma cruzi Chagas, Doença de Coração - doenças Galinha Background: The administration of anti-trypanosome nitroderivatives curtails Trypanosoma cruzi infection in Chagas disease patients, but does not prevent destructive lesions in the heart. This observation suggests that an effective treatment for the disease requires understanding its pathogenesis. Methodology/Principal Findings: To understand the origin of clinical manifestations of the heart disease we used a chicken model system in which infection can be initiated in the egg, but parasite persistence is precluded. T. cruzi inoculation into the air chamber of embryonated chicken eggs generated chicks that retained only the parasite mitochondrial kinetoplast DNA minicircle in their genome after eight days of gestation. Crossbreeding showed that minicircles were transferred vertically via the germ line to chicken progeny. Minicircle integration in coding regions was shown by targeted-primer thermal asymmetric interlaced PCR, and detected by direct genomic analysis. The kDNA-mutated chickens died with arrhythmias, shortness of breath, cyanosis and heart failure. These chickens with cardiomyopathy had rupture of the dystrophin and other genes that regulate cell growth and differentiation. Tissue pathology revealed inflammatory dilated cardiomegaly whereby immune system mononuclear cells lyse parasite-free target heart fibers. The heart cell destruction implicated a thymus-dependent, autoimmune; self-tissue rejection carried out by CD45+, CD8cd+, and CD8a lymphocytes. Conclusions/Significance: These results suggest that genetic alterations resulting from kDNA integration in the host genome lead to autoimmune-mediated destruction of heart tissue in the absence of T. cruzi parasites. 2019-02-06T15:38:25Z 2019-02-06T15:38:25Z 2011-03 Artigo Teixeira, Antonio R. L. et al. Trypanosoma cruzi in the chicken model: Chagas-like heart disease in the absence of parasitism. Plos Neglected Tropical Diseases, v. 5, n. 3, e1000, 2011. doi:10.1371/journal.pntd.0001000. Disponível em: https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0001000. Acesso em: 06 fev. 2019. http://repositorio.unb.br/handle/10482/33957 Inglês Acesso Aberto © 2011 Teixeira et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. application/pdf Plos
institution	REPOSITORIO UNB
collection	REPOSITORIO UNB
language	Inglês
topic	Tripanossoma cruzi Chagas, Doença de Coração - doenças Galinha
spellingShingle	Tripanossoma cruzi Chagas, Doença de Coração - doenças Galinha Teixeira, Antonio Raimundo Lima Cruz Gomes, Clever Nitz, Nadjar Sousa, Alessandro O. Alves, Rozeneide M. Guimaro, Maria C. Cordeiro, Ciro Bernal, Francisco M. Rosa, Ana de Cássia Hejnar, Jiri Leonardecz, Eduardo Hecht, Mariana M. Trypanosoma cruzi in the chicken model : Chagas-like heart disease in the absence of parasitism
description	Background: The administration of anti-trypanosome nitroderivatives curtails Trypanosoma cruzi infection in Chagas disease patients, but does not prevent destructive lesions in the heart. This observation suggests that an effective treatment for the disease requires understanding its pathogenesis. Methodology/Principal Findings: To understand the origin of clinical manifestations of the heart disease we used a chicken model system in which infection can be initiated in the egg, but parasite persistence is precluded. T. cruzi inoculation into the air chamber of embryonated chicken eggs generated chicks that retained only the parasite mitochondrial kinetoplast DNA minicircle in their genome after eight days of gestation. Crossbreeding showed that minicircles were transferred vertically via the germ line to chicken progeny. Minicircle integration in coding regions was shown by targeted-primer thermal asymmetric interlaced PCR, and detected by direct genomic analysis. The kDNA-mutated chickens died with arrhythmias, shortness of breath, cyanosis and heart failure. These chickens with cardiomyopathy had rupture of the dystrophin and other genes that regulate cell growth and differentiation. Tissue pathology revealed inflammatory dilated cardiomegaly whereby immune system mononuclear cells lyse parasite-free target heart fibers. The heart cell destruction implicated a thymus-dependent, autoimmune; self-tissue rejection carried out by CD45+, CD8cd+, and CD8a lymphocytes. Conclusions/Significance: These results suggest that genetic alterations resulting from kDNA integration in the host genome lead to autoimmune-mediated destruction of heart tissue in the absence of T. cruzi parasites.
format	Artigo
author	Teixeira, Antonio Raimundo Lima Cruz Gomes, Clever Nitz, Nadjar Sousa, Alessandro O. Alves, Rozeneide M. Guimaro, Maria C. Cordeiro, Ciro Bernal, Francisco M. Rosa, Ana de Cássia Hejnar, Jiri Leonardecz, Eduardo Hecht, Mariana M.
author_sort	Teixeira, Antonio Raimundo Lima Cruz
title	Trypanosoma cruzi in the chicken model : Chagas-like heart disease in the absence of parasitism
title_short	Trypanosoma cruzi in the chicken model : Chagas-like heart disease in the absence of parasitism
title_full	Trypanosoma cruzi in the chicken model : Chagas-like heart disease in the absence of parasitism
title_fullStr	Trypanosoma cruzi in the chicken model : Chagas-like heart disease in the absence of parasitism
title_full_unstemmed	Trypanosoma cruzi in the chicken model : Chagas-like heart disease in the absence of parasitism
title_sort	trypanosoma cruzi in the chicken model : chagas-like heart disease in the absence of parasitism
publisher	Plos
publishDate	2019
url	http://repositorio.unb.br/handle/10482/33957
_version_	1641988261463195648
score	13.657419

Trypanosoma cruzi in the chicken model : Chagas-like heart disease in the absence of parasitism

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