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

<h4>Background</h4>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...

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Autores principales:	Antonio R L Teixeira, Clever Gomes, Nadjar Nitz, Alessandro O Sousa, Rozeneide M Alves, Maria C Guimaro, Ciro Cordeiro, Francisco M Bernal, Ana C Rosa, Jiri Hejnar, Eduardo Leonardecz, Mariana M Hecht
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
Acceso en línea:	https://doaj.org/article/e77f8743521043178c263dfa06d9d255
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spelling	oai:doaj.org-article:e77f8743521043178c263dfa06d9d2552021-11-18T09:13:29ZTrypanosoma cruzi in the chicken model: Chagas-like heart disease in the absence of parasitism.1935-27271935-273510.1371/journal.pntd.0001000https://doaj.org/article/e77f8743521043178c263dfa06d9d2552011-03-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21468314/?tool=EBIhttps://doaj.org/toc/1935-2727https://doaj.org/toc/1935-2735<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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(+), CD8γδ(+), and CD8α lymphocytes.<h4>Conclusions/significance</h4>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.Antonio R L TeixeiraClever GomesNadjar NitzAlessandro O SousaRozeneide M AlvesMaria C GuimaroCiro CordeiroFrancisco M BernalAna C RosaJiri HejnarEduardo LeonardeczMariana M HechtPublic Library of Science (PLoS)articleArctic medicine. Tropical medicineRC955-962Public aspects of medicineRA1-1270ENPLoS Neglected Tropical Diseases, Vol 5, Iss 3, p e1000 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
spellingShingle	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Antonio R L Teixeira Clever Gomes Nadjar Nitz Alessandro O Sousa Rozeneide M Alves Maria C Guimaro Ciro Cordeiro Francisco M Bernal Ana C Rosa Jiri Hejnar Eduardo Leonardecz Mariana M Hecht Trypanosoma cruzi in the chicken model: Chagas-like heart disease in the absence of parasitism.
description	<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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(+), CD8γδ(+), and CD8α lymphocytes.<h4>Conclusions/significance</h4>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	article
author	Antonio R L Teixeira Clever Gomes Nadjar Nitz Alessandro O Sousa Rozeneide M Alves Maria C Guimaro Ciro Cordeiro Francisco M Bernal Ana C Rosa Jiri Hejnar Eduardo Leonardecz Mariana M Hecht
author_facet	Antonio R L Teixeira Clever Gomes Nadjar Nitz Alessandro O Sousa Rozeneide M Alves Maria C Guimaro Ciro Cordeiro Francisco M Bernal Ana C Rosa Jiri Hejnar Eduardo Leonardecz Mariana M Hecht
author_sort	Antonio R L Teixeira
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	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/e77f8743521043178c263dfa06d9d255
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Trypanosoma cruzi in the chicken model: Chagas-like heart disease in the absence of parasitism.

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