Laboratório de Biologia das Interações Celulares, Departamento de Morfologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
Programa de Pós-Graduação em Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
Hum Immunol. 2019 Jul;80(7):517-522. doi: 10.1016/j.humimm.2019.03.009. Epub 2019 Mar 7.
Chagas disease, caused by the protozoan Trypanosoma cruzi (T. cruzi), is the fourth most important tropical disease, which affects approximately 7 million people worldwide. The mechanisms involved in the development of this disease are not completely well understood. An important protective role of regulatory T cells (Treg) in Chagas disease has been observed; however, the specific mechanisms remain unclear. We evaluated apoptosis as a possible mechanism mediated by Treg cells (CD4CD25FOXP3) to orchestrate the immune response in chronic Chagas disease.
Patients with Chagas disease were grouped as the indeterminate (IND; asymptomatic patients with Chagas disease; n = 10) and dilated cardiomyopathy (CARD; n = 10). Healthy T. cruzi-negative individuals (NI; n = 10) were included as a control group. In order to evaluate the apoptotic cell profile, the expression of PD1, PD1L, CD39, CD95, CD95L molecules were investigated. We also evaluated the proportion of CD14 cells expressing caspase 3. The IND group presented a substantially higher expression of CD39 by Treg cells as compared to the CARD group. On the other hand, the CARD group showed higher expression of PD-1 by Treg cells than both NI and IND groups. Significant positive correlations were observed between Treg CD95L cells and CD14 cells expressing caspase 3 as well as between Treg CD39 cells and CD14 Caspase3 cells in the IND group.
Our data indicate that the expressions of different molecules that induce apoptosis are associated with suppressive mechanisms mediated by Treg cells and suggest a possible role for PD1 and PDL1 molecules in the morbidity of chronic Chagas disease.
恰加斯病由原生动物克氏锥虫（T. cruzi）引起，是第四大重要热带病，全球约有 700 万人受到影响。该病的发病机制尚未完全阐明。调节性 T 细胞（Treg）在恰加斯病中具有重要的保护作用，但具体机制尚不清楚。我们评估了细胞凋亡作为 Treg 细胞（CD4CD25FOXP3）介导的、调节慢性恰加斯病免疫反应的一种可能机制。
将恰加斯病患者分为未确定型（IND；无症状恰加斯病患者；n=10）和扩张型心肌病型（CARD；n=10）。纳入健康的克氏锥虫阴性个体（NI；n=10）作为对照组。为了评估凋亡细胞的表型，检测了 PD1、PD1L、CD39、CD95、CD95L 分子的表达情况。我们还评估了表达半胱氨酸蛋白酶 3 的 CD14 细胞的比例。与 CARD 组相比，IND 组 Treg 细胞表达 CD39 的水平显著升高。另一方面，CARD 组 Treg 细胞表达 PD-1 的水平高于 NI 组和 IND 组。在 IND 组中，Treg CD95L 细胞与表达半胱氨酸蛋白酶 3 的 CD14 细胞之间以及 Treg CD39 细胞与 CD14 半胱氨酸蛋白酶 3 细胞之间存在显著正相关。
我们的数据表明，诱导凋亡的不同分子的表达与 Treg 细胞介导的抑制机制相关，并提示 PD1 和 PDL1 分子可能在慢性恰加斯病的发病机制中发挥作用。
