T-Cell Subpopulations Exhibit Distinct Recruitment Potential, Immunoregulatory Profile and Functional Characteristics in Chagas versus Idiopathic Dilated Cardiomyopathies

Frontiers in Cardiovascular Medicine

article

Fernanda Villani¹  Janete Soares Coelho¹  Claudia Ida Brodskyn⁴  Andrea Teixeira⁵  Kenneth J. Gollob⁶  Maria do Carmo P. Nunes⁸  Walderez O. Dutra¹  Eula G. A. Neves¹  Carolina C. Koh¹  Thaiany G. Souza-Silva¹  Lívia Silva Araújo Passos¹  Ana Carolina C. Silva¹  Teresiama Velikkakam¹ 

[1] Department of Morphology, Cell-Cell Interactions Laboratory, Institute of Biological Sciences, Federal University of Minas Gerais;Minas Gerais State University;Ezequiel Dias Foundation;Gonçalo Moniz Research Center;Rene Rachou Institute;Hospital Israelita Albert Einstein;Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais, INCT-DT;Graduate Program in Infectology and Tropical Medicine, School of Medicine, Federal University of Minas Gerais;Brigham and Womens Hospital, Harvard University

关键词: T-cells;    cytokines;    chemokines;    inflammation;    Chagas cardiomyopathy;    idiopathic cardiomyopathy;   

DOI  :  10.3389/fcvm.2022.787423

学科分类：地球科学(综合)

来源: Frontiers

【 摘 要 】

Chronic Chagas cardiomyopathy (CCC) is one of the deadliest cardiomyopathies known and the most severe manifestation of Chagas disease, which is caused by infection with the parasite Trypanosoma cruzi . Idiopathic dilated cardiomyopathies (IDC) are a diverse group of inflammatory heart diseases that affect the myocardium and are clinically similar to CCC, often causing heart failure and death. While T-cells are critical for mediating cardiac pathology in CCC and IDC, the mechanisms underlying T-cell function in these cardiomyopathies are not well-defined. In this study, we sought to investigate the phenotypic and functional characteristics of T-cell subpopulations in CCC and IDC, aiming to clarify whether the inflammatory response is similar or distinct in these cardiomyopathies. We evaluated the expression of systemic cytokines, determined the sources of the different cytokines, the expression of their receptors, of cytotoxic molecules, and of molecules associated with recruitment to the heart by circulating CD4 + , CD8 + , and CD4-CD8- T-cells from CCC and IDC patients, using multiparameter flow cytometry combined with conventional and unsupervised machine-learning strategies. We also used an in silico approach to identify the expression of genes that code for key molecules related to T-cell function in hearts of patient with CCC and IDC. Our data demonstrated that CCC patients displayed a more robust systemic inflammatory cytokine production as compared to IDC. While CD8 + T-cells were highly activated in CCC as compared to IDC, CD4 + T-cells were more activated in IDC. In addition to differential expression of functional molecules, these cells also displayed distinct expression of molecules associated with recruitment to the heart. In silico analysis of gene transcripts in the cardiac tissue demonstrated a significant correlation between CD8 and inflammatory, cytotoxic and cardiotropic molecules in CCC transcripts, while no correlation with CD4 was observed. A positive correlation was observed between CD4 and perforin transcripts in hearts from IDC but not CCC, as compared to normal tissue. These data show a clearly distinct systemic and local cellular response in CCC and IDC, despite their similar cardiac impairment, which may contribute to identifying specific immunotherapeutic targets in these diseases.

【 授权许可】

CC BY