The Characterization of Cardiac Explants Reveals Unique Fibrosis Patterns and a Predominance of CD8+ T Cell Subpopulations in Patients with Chronic Chagas Cardiomyopathy

Aim: The present study aimed to characterize the histopathological findings and the phenotype of inflammatory cells in the myocardial tissue of patients with end-stage heart failure (ESHF) secondary to CCC in comparison with ESHF secondary to non-Chagas cardiomyopathies (NCC). Methods: A total of 32...

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Main Authors: Martha Lucía Díaz, Fredy A. Delgado, Ruth A Martínez, Mayra Alejandra Jaimes, Luis Eduardo Echeverría, Sergio Alejandro Gómez-Ochoa, Julio César Mantilla-Hernández, Clara Isabel González
Format: Article
Language:English
Published: MDPI AG 2022-11-01
Series:Pathogens
Subjects:
Online Access:https://www.mdpi.com/2076-0817/11/12/1402
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author Martha Lucía Díaz
Fredy A. Delgado
Ruth A Martínez
Mayra Alejandra Jaimes
Luis Eduardo Echeverría
Sergio Alejandro Gómez-Ochoa
Julio César Mantilla-Hernández
Clara Isabel González
author_facet Martha Lucía Díaz
Fredy A. Delgado
Ruth A Martínez
Mayra Alejandra Jaimes
Luis Eduardo Echeverría
Sergio Alejandro Gómez-Ochoa
Julio César Mantilla-Hernández
Clara Isabel González
author_sort Martha Lucía Díaz
collection DOAJ
description Aim: The present study aimed to characterize the histopathological findings and the phenotype of inflammatory cells in the myocardial tissue of patients with end-stage heart failure (ESHF) secondary to CCC in comparison with ESHF secondary to non-Chagas cardiomyopathies (NCC). Methods: A total of 32 explanted hearts were collected from transplanted patients between 2014 and 2017. Of these, 21 were classified as CCC and 11 as other NCC. A macroscopic analysis followed by a microscopic analysis were performed. Finally, the phenotypes of the inflammatory infiltrates were characterized using flow cytometry. Results: Microscopic analysis revealed more extensive fibrotic involvement in patients with CCC, with more frequent foci of fibrosis, collagen deposits, and degeneration of myocardial fibers, in addition to identifying foci of inflammatory infiltrate of greater magnitude. Finally, cell phenotyping identified more memory T cells, mainly CD8+CD45RO+ T cells, and fewer transitioning T cells (CD45RA+/CD45RO+) in patients with CCC compared with the NCC group. Conclusions: CCC represents a unique form of myocardial involvement characterized by abundant inflammatory infiltrates, severe interstitial fibrosis, extensive collagen deposits, and marked cardiomyocyte degeneration. The structural myocardial changes observed in late-stage Chagas cardiomyopathy appear to be closely related to the presence of cardiac fibrosis and the colocalization of collagen fibers and inflammatory cells, a finding that serves as a basis for the generation of new hypotheses aimed at better understanding the role of inflammation and fibrogenesis in the progression of CCC. Finally, the predominance of memory T cells in CCC compared with NCC hearts highlights the critical role of the parasite-specific lymphocytic response in the course of the infection.
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spelling doaj.art-7f32f115d9be49d48d8abc27c0caed1f2023-11-24T17:12:04ZengMDPI AGPathogens2076-08172022-11-011112140210.3390/pathogens11121402The Characterization of Cardiac Explants Reveals Unique Fibrosis Patterns and a Predominance of CD8+ T Cell Subpopulations in Patients with Chronic Chagas CardiomyopathyMartha Lucía Díaz0Fredy A. Delgado1Ruth A Martínez2Mayra Alejandra Jaimes3Luis Eduardo Echeverría4Sergio Alejandro Gómez-Ochoa5Julio César Mantilla-Hernández6Clara Isabel González7Immunology and Molecular Epidemiology Group, School of Microbiology, Universidad Industrial de Santander, Bucaramanga 680002, ColombiaImmunology and Molecular Epidemiology Group, School of Microbiology, Universidad Industrial de Santander, Bucaramanga 680002, ColombiaImmunology and Molecular Epidemiology Group, School of Microbiology, Universidad Industrial de Santander, Bucaramanga 680002, ColombiaImmunology and Molecular Epidemiology Group, School of Microbiology, Universidad Industrial de Santander, Bucaramanga 680002, ColombiaHeart Failure Clinic, Fundación Cardiovascular de Colombia, Floridablanca 681004, ColombiaHeart Failure Clinic, Fundación Cardiovascular de Colombia, Floridablanca 681004, ColombiaDepartment of Pathology, Universidad Industrial de Santander, Bucaramanga 680002, ColombiaImmunology and Molecular Epidemiology Group, School of Microbiology, Universidad Industrial de Santander, Bucaramanga 680002, ColombiaAim: The present study aimed to characterize the histopathological findings and the phenotype of inflammatory cells in the myocardial tissue of patients with end-stage heart failure (ESHF) secondary to CCC in comparison with ESHF secondary to non-Chagas cardiomyopathies (NCC). Methods: A total of 32 explanted hearts were collected from transplanted patients between 2014 and 2017. Of these, 21 were classified as CCC and 11 as other NCC. A macroscopic analysis followed by a microscopic analysis were performed. Finally, the phenotypes of the inflammatory infiltrates were characterized using flow cytometry. Results: Microscopic analysis revealed more extensive fibrotic involvement in patients with CCC, with more frequent foci of fibrosis, collagen deposits, and degeneration of myocardial fibers, in addition to identifying foci of inflammatory infiltrate of greater magnitude. Finally, cell phenotyping identified more memory T cells, mainly CD8+CD45RO+ T cells, and fewer transitioning T cells (CD45RA+/CD45RO+) in patients with CCC compared with the NCC group. Conclusions: CCC represents a unique form of myocardial involvement characterized by abundant inflammatory infiltrates, severe interstitial fibrosis, extensive collagen deposits, and marked cardiomyocyte degeneration. The structural myocardial changes observed in late-stage Chagas cardiomyopathy appear to be closely related to the presence of cardiac fibrosis and the colocalization of collagen fibers and inflammatory cells, a finding that serves as a basis for the generation of new hypotheses aimed at better understanding the role of inflammation and fibrogenesis in the progression of CCC. Finally, the predominance of memory T cells in CCC compared with NCC hearts highlights the critical role of the parasite-specific lymphocytic response in the course of the infection.https://www.mdpi.com/2076-0817/11/12/1402chagas diseasechronic chagas cardiomyopathyhistopathologyimmunophenotyping
spellingShingle Martha Lucía Díaz
Fredy A. Delgado
Ruth A Martínez
Mayra Alejandra Jaimes
Luis Eduardo Echeverría
Sergio Alejandro Gómez-Ochoa
Julio César Mantilla-Hernández
Clara Isabel González
The Characterization of Cardiac Explants Reveals Unique Fibrosis Patterns and a Predominance of CD8+ T Cell Subpopulations in Patients with Chronic Chagas Cardiomyopathy
Pathogens
chagas disease
chronic chagas cardiomyopathy
histopathology
immunophenotyping
title The Characterization of Cardiac Explants Reveals Unique Fibrosis Patterns and a Predominance of CD8+ T Cell Subpopulations in Patients with Chronic Chagas Cardiomyopathy
title_full The Characterization of Cardiac Explants Reveals Unique Fibrosis Patterns and a Predominance of CD8+ T Cell Subpopulations in Patients with Chronic Chagas Cardiomyopathy
title_fullStr The Characterization of Cardiac Explants Reveals Unique Fibrosis Patterns and a Predominance of CD8+ T Cell Subpopulations in Patients with Chronic Chagas Cardiomyopathy
title_full_unstemmed The Characterization of Cardiac Explants Reveals Unique Fibrosis Patterns and a Predominance of CD8+ T Cell Subpopulations in Patients with Chronic Chagas Cardiomyopathy
title_short The Characterization of Cardiac Explants Reveals Unique Fibrosis Patterns and a Predominance of CD8+ T Cell Subpopulations in Patients with Chronic Chagas Cardiomyopathy
title_sort characterization of cardiac explants reveals unique fibrosis patterns and a predominance of cd8 t cell subpopulations in patients with chronic chagas cardiomyopathy
topic chagas disease
chronic chagas cardiomyopathy
histopathology
immunophenotyping
url https://www.mdpi.com/2076-0817/11/12/1402
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