Grupo de Ciencias Básicas Médicas, School of Medicine, Universidad de los Andes, Bogotá, Colombia.
Department of Biological Sciences, School of Sciences, Universidad de los Andes, Bogotá, Colombia.
Front Immunol. 2019 Jul 19;10:1671. doi: 10.3389/fimmu.2019.01671. eCollection 2019.
Monocytes are classified according to their CD14 and CD16 expression into classical (reparative), intermediate (inflammatory), and non-classical. This study assessed the frequency of monocyte and the relationship between monocyte subset percentages and the levels of blood cytokines in Colombian chagasic patients with different clinical forms. This study included chagasic patients in different clinical stages: indeterminate (IND) = 14, chronic chagasic cardiomyopathy (CCC) = 14, and heart transplant chagasic (HTCC) = 9; controls with non-chagasic cardiopathy (NCC) = 15, and healthy individuals (HI) = 15. Peripheral blood mononuclear cells (PBMCs) were isolated, labeled for CD14, CD16, and HLA-DR, and analyzed by flow cytometry. Cytokines were measured with a bead-based immunoassay. Percentages of total CD14+ CD16+ and CD14+ HLA-DR+ monocytes were higher in patients with heart involvement (CCC, HTCC, and NCC) than controls. Percentages of intermediate monocytes increased in symptomatic chagasic patients (CCC and HTCC) compared to asymptomatic chagasic patients (IND) and controls (HI). Asymptomatic chagasic patients (IND) had higher percentages of classical monocytes, an increased production of CCL17 chemokine compared to chagasic symptomatic patients (CCC), and their levels of CCL17 was positively correlated with the percentage of classical monocyte subset. In CCC, the percentages of intermediate and classical monocytes were positively correlated with IL-6 levels, which were higher in this group compared to HI, and negatively with IL-12p40 concentration, respectively. Remarkably, there also was an important increased of classical monocytes frequency in three chronic chagasic patients who underwent cardiac transplant, of which one received anti-parasitic treatment. Our findings suggest that cardiac chagasic patients have an increased percentage of inflammatory monocytes and produce more IL-6, a biomarker of heart failure and left ventricular dysfunction, whereas asymptomatic chagasic individuals present a higher percentage of reparative monocytes and CCL17.
单核细胞根据其 CD14 和 CD16 的表达水平分为经典型（修复型）、中间型（炎症型）和非经典型。本研究评估了不同临床形式的哥伦比亚恰加斯病患者单核细胞的频率及其与血液细胞因子水平之间的关系。本研究包括不同临床阶段的恰加斯病患者：未确定（IND）=14 例，慢性恰加斯心肌病（CCC）=14 例，心脏移植恰加斯（HTCC）=9 例；非恰加斯心脏病对照组（NCC）=15 例，健康对照组（HI）=15 例。分离外周血单核细胞（PBMC），用 CD14、CD16 和 HLA-DR 进行标记，并用流式细胞术进行分析。用基于珠的免疫测定法测量细胞因子。有心脏受累的患者（CCC、HTCC 和 NCC）的总 CD14+CD16+和 CD14+HLA-DR+单核细胞的百分比高于对照组。有症状的恰加斯病患者（CCC 和 HTCC）的中间单核细胞百分比增加，与无症状的恰加斯病患者（IND）和对照组（HI）相比。无症状的恰加斯病患者（IND）的经典单核细胞百分比较高，与有症状的恰加斯病患者（CCC）相比，趋化因子 CCL17 的产生增加，其 CCL17 水平与经典单核细胞亚群的百分比呈正相关。在 CCC 中，中间和经典单核细胞的百分比与 IL-6 水平呈正相关，与 HI 相比，该组的 IL-6 水平较高，与 IL-12p40 浓度呈负相关。值得注意的是，在接受心脏移植的三名慢性恰加斯病患者中，经典单核细胞的频率也显著增加，其中一名患者接受了抗寄生虫治疗。我们的研究结果表明，心脏恰加斯病患者的炎症性单核细胞百分比增加，并且产生更多的 IL-6，这是心力衰竭和左心室功能障碍的生物标志物，而无症状的恰加斯病患者则表现出更高的修复性单核细胞和 CCL17 百分比。
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