Programa Biología Celular y Molecular, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
Instituto de Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Santiago, Chile.
Oxid Med Cell Longev. 2021 Dec 23;2021:4993452. doi: 10.1155/2021/4993452. eCollection 2021.
Chagas disease is a neglected tropical disease caused by the flagellated protozoa that affects several million people mainly in Latin American countries. Chagas disease has two phases, which are acute and chronic, both separated by an indeterminate time period in which the infected individual is relatively asymptomatic. The acute phase extends for 40-60 days with atypical and mild symptoms; however, about 30% of the infected patients will develop a symptomatic chronic phase, which is characterized by either cardiac, digestive, neurological, or endocrine problems. Cardiomyopathy is the most important and severe result of Chagas disease, which leads to left ventricular systolic dysfunction, heart failure, and sudden cardiac death. Most deaths are due to heart failure (70%) and sudden death (30%) resulting from cardiomyopathy. During the chronic phase, -infected macrophages respond with the production of proinflammatory cytokines and production of superoxide and nitric oxide by the NADPH oxidase 2 (NOX2) and inducible nitric oxide synthase (iNOS) enzymes, respectively. During the chronic phase, myocardial changes are produced as a result of chronic inflammation, oxidative stress, fibrosis, and cell death. The cellular inflammatory response is mainly the result of activation of the NF-B-dependent pathway, which activates gene expression of inflammatory cytokines, leading to progressive tissue damage. The persisting production of reactive oxygen species (ROS) is the result of mitochondrial dysfunction in the cardiomyocytes. In this review, we will discuss inflammation and oxidative damage which is produced in the heart during the chronic phase of Chagas disease and recent evidence on the role of macrophages and the production of proinflammatory cytokines during the acute phase and the origin of macrophages/monocytes during the chronic phase of Chagas disease. We will also discuss the contributing factors and mechanisms leading to the chronic inflammation of the cardiac tissue during the chronic phase of the disease as well as the innate and adaptive host immune response. The contribution of genetic factors to the progression of the chronic inflammatory cardiomyopathy of chronic Chagas disease is also discussed. The secreted extracellular vesicles (exosomes) produced for both and infected host cells can play key roles in the host immune response, and those roles are described. Lastly, we describe potential treatments to attenuate the chronic inflammation of the cardiac tissue, designed to improve heart function in chagasic patients.
恰加斯病是一种被忽视的热带病，由鞭毛原生动物引起，主要影响拉丁美洲国家的数百万人。恰加斯病有两个阶段，即急性和慢性，两者之间间隔一段时间，在此期间受感染者相对无症状。急性阶段持续 40-60 天，症状不典型且轻微；然而，约 30%的受感染者将发展为有症状的慢性期，其特征为心脏、消化、神经或内分泌问题。心肌病是恰加斯病最重要和最严重的结果，导致左心室收缩功能障碍、心力衰竭和心脏性猝死。大多数死亡是由于心力衰竭（70%）和心肌病导致的心脏性猝死（30%）。在慢性期，感染的巨噬细胞通过 NADPH 氧化酶 2（NOX2）和诱导型一氧化氮合酶（iNOS）酶分别产生促炎细胞因子和产生超氧化物和一氧化氮来作出反应。在慢性期，由于慢性炎症、氧化应激、纤维化和细胞死亡，心肌发生变化。细胞炎症反应主要是 NF-B 依赖性途径激活的结果，该途径激活炎症细胞因子的基因表达，导致进行性组织损伤。活性氧物质（ROS）的持续产生是心肌细胞中线粒体功能障碍的结果。在这篇综述中，我们将讨论恰加斯病慢性期心脏中产生的炎症和氧化损伤，以及巨噬细胞和促炎细胞因子在急性期的产生以及恰加斯病慢性期巨噬细胞/单核细胞的起源的最新证据。我们还将讨论导致疾病慢性期心肌组织慢性炎症的促成因素和机制，以及先天和适应性宿主免疫反应。还讨论了遗传因素对慢性恰加斯病慢性炎症性心肌病进展的贡献。和受感染宿主细胞产生的分泌细胞外囊泡（外泌体）在宿主免疫反应中可以发挥关键作用，并且描述了这些作用。最后，我们描述了潜在的治疗方法来减轻心脏组织的慢性炎症，旨在改善恰加斯病患者的心脏功能。
