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心脏外植体的特征揭示了慢性恰加斯心肌病患者独特的纤维化模式和CD8 + T细胞亚群的优势。

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

作者信息

Díaz Martha Lucía, Delgado Fredy A, Martínez Ruth A, Jaimes Mayra Alejandra, Echeverría Luis Eduardo, Gómez-Ochoa Sergio Alejandro, Mantilla-Hernández Julio César, González Clara Isabel

机构信息

Immunology and Molecular Epidemiology Group, School of Microbiology, Universidad Industrial de Santander, Bucaramanga 680002, Colombia.

Heart Failure Clinic, Fundación Cardiovascular de Colombia, Floridablanca 681004, Colombia.

出版信息

Pathogens. 2022 Nov 23;11(12):1402. doi: 10.3390/pathogens11121402.

Abstract

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.

摘要

目的

本研究旨在对恰加斯心肌病(CCC)继发的终末期心力衰竭(ESHF)患者与非恰加斯心肌病(NCC)继发的ESHF患者心肌组织的组织病理学发现及炎症细胞表型进行特征描述。

方法

2014年至2017年间,从移植患者中收集了32颗移植心脏。其中,21颗被归类为CCC,11颗为其他NCC。进行了宏观分析,随后进行微观分析。最后,使用流式细胞术对炎症浸润的表型进行特征描述。

结果

微观分析显示,CCC患者的纤维化累及范围更广,纤维化灶、胶原沉积和心肌纤维变性更常见,此外还发现了更大范围的炎症浸润灶。最后,细胞表型分析发现,与NCC组相比,CCC患者的记忆T细胞更多,主要是CD8+CD45RO+T细胞,而过渡性T细胞(CD45RA+/CD45RO+)更少。

结论

CCC代表了一种独特的心肌受累形式,其特征为丰富的炎症浸润、严重的间质纤维化、广泛的胶原沉积和明显的心肌细胞变性。恰加斯心肌病晚期观察到的心肌结构变化似乎与心脏纤维化的存在以及胶原纤维和炎症细胞的共定位密切相关,这一发现为生成旨在更好理解炎症和纤维生成在CCC进展中作用的新假说奠定了基础。最后,与NCC心脏相比,CCC中记忆T细胞的优势突出了寄生虫特异性淋巴细胞反应在感染过程中的关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b1e/9788058/2c9914a1b1ef/pathogens-11-01402-g001.jpg

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