Inhibition of autoimmune Chagas-like heart disease by bone marrow transplantation.
BACKGROUND:Infection with the protozoan Trypanosoma cruzi manifests in mammals as Chagas heart disease. The treatment available for chagasic cardiomyopathy is unsatisfactory. METHODS/PRINCIPAL FINDINGS:To study the disease pathology and its inhibition, we employed a syngeneic chicken model refractor...
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ftdoajarticles:oai:doaj.org/article:acfc02fbda39488099ee5ea0231ebd11 2023-05-15T15:11:41+02:00 Inhibition of autoimmune Chagas-like heart disease by bone marrow transplantation. Maria C Guimaro Rozeneide M Alves Ester Rose Alessandro O Sousa Ana de Cássia Rosa Mariana M Hecht Marcelo V Sousa Rafael R Andrade Tamires Vital Jiří Plachy Nadjar Nitz Jiří Hejnar Clever C Gomes Antonio R L Teixeira 2014-12-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0003384 https://doaj.org/article/acfc02fbda39488099ee5ea0231ebd11 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC4270743?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0003384 https://doaj.org/article/acfc02fbda39488099ee5ea0231ebd11 PLoS Neglected Tropical Diseases, Vol 8, Iss 12, p e3384 (2014) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2014 ftdoajarticles https://doi.org/10.1371/journal.pntd.0003384 2022-12-31T00:34:12Z BACKGROUND:Infection with the protozoan Trypanosoma cruzi manifests in mammals as Chagas heart disease. The treatment available for chagasic cardiomyopathy is unsatisfactory. METHODS/PRINCIPAL FINDINGS:To study the disease pathology and its inhibition, we employed a syngeneic chicken model refractory to T. cruzi in which chickens hatched from T. cruzi inoculated eggs retained parasite kDNA (1.4 kb) minicircles. Southern blotting with EcoRI genomic DNA digests revealed main 18 and 20 kb bands by hybridization with a radiolabeled minicircle sequence. Breeding these chickens generated kDNA-mutated F1, F2, and F3 progeny. A targeted-primer TAIL-PCR (tpTAIL-PCR) technique was employed to detect the kDNA integrations. Histocompatible reporter heart grafts were used to detect ongoing inflammatory cardiomyopathy in kDNA-mutated chickens. Fluorochromes were used to label bone marrow CD3+, CD28+, and CD45+ precursors of the thymus-dependent CD8α+ and CD8β+ effector cells that expressed TCRγδ, vβ1 and vβ2 receptors, which infiltrated the adult hearts and the reporter heart grafts. CONCLUSIONS/SIGNIFICANCE:Genome modifications in kDNA-mutated chickens can be associated with disruption of immune tolerance to compatible heart grafts and with rejection of the adult host's heart and reporter graft, as well as tissue destruction by effector lymphocytes. Autoimmune heart rejection was largely observed in chickens with kDNA mutations in retrotransposons and in coding genes with roles in cell structure, metabolism, growth, and differentiation. Moreover, killing the sick kDNA-mutated bone marrow cells with cytostatic and anti-folate drugs and transplanting healthy marrow cells inhibited heart rejection. We report here for the first time that healthy bone marrow cells inhibited heart pathology in kDNA+ chickens and thus prevented the genetically driven clinical manifestations of the disease. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 8 12 e3384 |
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Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
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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 Maria C Guimaro Rozeneide M Alves Ester Rose Alessandro O Sousa Ana de Cássia Rosa Mariana M Hecht Marcelo V Sousa Rafael R Andrade Tamires Vital Jiří Plachy Nadjar Nitz Jiří Hejnar Clever C Gomes Antonio R L Teixeira Inhibition of autoimmune Chagas-like heart disease by bone marrow transplantation. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
BACKGROUND:Infection with the protozoan Trypanosoma cruzi manifests in mammals as Chagas heart disease. The treatment available for chagasic cardiomyopathy is unsatisfactory. METHODS/PRINCIPAL FINDINGS:To study the disease pathology and its inhibition, we employed a syngeneic chicken model refractory to T. cruzi in which chickens hatched from T. cruzi inoculated eggs retained parasite kDNA (1.4 kb) minicircles. Southern blotting with EcoRI genomic DNA digests revealed main 18 and 20 kb bands by hybridization with a radiolabeled minicircle sequence. Breeding these chickens generated kDNA-mutated F1, F2, and F3 progeny. A targeted-primer TAIL-PCR (tpTAIL-PCR) technique was employed to detect the kDNA integrations. Histocompatible reporter heart grafts were used to detect ongoing inflammatory cardiomyopathy in kDNA-mutated chickens. Fluorochromes were used to label bone marrow CD3+, CD28+, and CD45+ precursors of the thymus-dependent CD8α+ and CD8β+ effector cells that expressed TCRγδ, vβ1 and vβ2 receptors, which infiltrated the adult hearts and the reporter heart grafts. CONCLUSIONS/SIGNIFICANCE:Genome modifications in kDNA-mutated chickens can be associated with disruption of immune tolerance to compatible heart grafts and with rejection of the adult host's heart and reporter graft, as well as tissue destruction by effector lymphocytes. Autoimmune heart rejection was largely observed in chickens with kDNA mutations in retrotransposons and in coding genes with roles in cell structure, metabolism, growth, and differentiation. Moreover, killing the sick kDNA-mutated bone marrow cells with cytostatic and anti-folate drugs and transplanting healthy marrow cells inhibited heart rejection. We report here for the first time that healthy bone marrow cells inhibited heart pathology in kDNA+ chickens and thus prevented the genetically driven clinical manifestations of the disease. |
format |
Article in Journal/Newspaper |
author |
Maria C Guimaro Rozeneide M Alves Ester Rose Alessandro O Sousa Ana de Cássia Rosa Mariana M Hecht Marcelo V Sousa Rafael R Andrade Tamires Vital Jiří Plachy Nadjar Nitz Jiří Hejnar Clever C Gomes Antonio R L Teixeira |
author_facet |
Maria C Guimaro Rozeneide M Alves Ester Rose Alessandro O Sousa Ana de Cássia Rosa Mariana M Hecht Marcelo V Sousa Rafael R Andrade Tamires Vital Jiří Plachy Nadjar Nitz Jiří Hejnar Clever C Gomes Antonio R L Teixeira |
author_sort |
Maria C Guimaro |
title |
Inhibition of autoimmune Chagas-like heart disease by bone marrow transplantation. |
title_short |
Inhibition of autoimmune Chagas-like heart disease by bone marrow transplantation. |
title_full |
Inhibition of autoimmune Chagas-like heart disease by bone marrow transplantation. |
title_fullStr |
Inhibition of autoimmune Chagas-like heart disease by bone marrow transplantation. |
title_full_unstemmed |
Inhibition of autoimmune Chagas-like heart disease by bone marrow transplantation. |
title_sort |
inhibition of autoimmune chagas-like heart disease by bone marrow transplantation. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2014 |
url |
https://doi.org/10.1371/journal.pntd.0003384 https://doaj.org/article/acfc02fbda39488099ee5ea0231ebd11 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 8, Iss 12, p e3384 (2014) |
op_relation |
http://europepmc.org/articles/PMC4270743?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0003384 https://doaj.org/article/acfc02fbda39488099ee5ea0231ebd11 |
op_doi |
https://doi.org/10.1371/journal.pntd.0003384 |
container_title |
PLoS Neglected Tropical Diseases |
container_volume |
8 |
container_issue |
12 |
container_start_page |
e3384 |
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1766342509362937856 |