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. Me...
Published in: | PLoS Neglected Tropical Diseases |
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ftdoajarticles:oai:doaj.org/article:e77f8743521043178c263dfa06d9d255 2023-05-15T15:09:49+02:00 Trypanosoma cruzi in the chicken model: Chagas-like heart disease in the absence of parasitism. 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 2011-03-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0001000 https://doaj.org/article/e77f8743521043178c263dfa06d9d255 EN eng Public Library of Science (PLoS) https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21468314/?tool=EBI https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0001000 https://doaj.org/article/e77f8743521043178c263dfa06d9d255 PLoS Neglected Tropical Diseases, Vol 5, Iss 3, p e1000 (2011) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2011 ftdoajarticles https://doi.org/10.1371/journal.pntd.0001000 2022-12-31T09:00:55Z 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(+), CD8γδ(+), and CD8α 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. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 5 3 e1000 |
institution |
Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
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. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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(+), CD8γδ(+), and CD8α 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 |
Article in Journal/Newspaper |
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://doi.org/10.1371/journal.pntd.0001000 https://doaj.org/article/e77f8743521043178c263dfa06d9d255 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 5, Iss 3, p e1000 (2011) |
op_relation |
https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21468314/?tool=EBI https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0001000 https://doaj.org/article/e77f8743521043178c263dfa06d9d255 |
op_doi |
https://doi.org/10.1371/journal.pntd.0001000 |
container_title |
PLoS Neglected Tropical Diseases |
container_volume |
5 |
container_issue |
3 |
container_start_page |
e1000 |
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1766340934509789184 |