背景:弓形虫(T。gondii)再激活是常见的,尤其是在免疫受损的个体中,如艾滋病患者。与弓形虫病相关的心脏受累,然而,通常被神经系统恶化所掩盖。这项研究的目的是观察感染后各个里程碑时期心脏功能的变化,并评估再激活是否会更严重地损害心脏。
方法:我们使用中国流行的弓形虫主要品系TgCtwh6建立了三种小鼠感染模型。这些组包括急性组,慢性潜伏群体,并重新激活组。我们通过H&E染色评估心功能损伤,Masson染色,超声心动图,心肌酶谱,和心肌肌钙蛋白,免疫印迹法检测炎症因子和抗氧化因子的表达。免疫荧光法检测巨噬细胞标记物F4/80的表达。
结果:我们的结果表明,急性和再激活组发生了心脏损伤。心脏功能受损表现为心率降低和左心室收缩功能代偿性增加。血清心肌酶水平也急剧增加。在慢性期,心肌纤维化发展,舒张功能严重受损,炎症持续存在,巨噬细胞表达略有降低。最终,再激活感染加剧了小鼠心脏功能的损害,有可能导致舒张性心力衰竭.巨噬细胞被强烈激活,心肌纤维化加重。此外,感染严重影响了心脏的抗氧化能力。
结论:综合来看,这些结果表明弓形虫感染的重新激活可以加重对心脏的伤害,这可能与宿主细胞介导的免疫反应和巨噬细胞产生强烈的细胞因子有关,从而代表了对弓形虫病致病机制的新见解。
BACKGROUND: Toxoplasma gondii (T. gondii) reactivation is common, especially among immunocompromised individuals, such as AIDS patients. The cardiac involvement associated with toxoplasmosis, however, is usually obscured by neurological deterioration. The aim of this study was to observe the alterations in cardiac functions in various landmark periods after infection and to assess whether reactivation more seriously damages the heart.
METHODS: We established three infection models in mice using TgCtwh6, a major strain of T. gondii prevalent in China. The groups included an acute group, chronic latent group, and reactivation group. We evaluated the cardiac function impairment via H & E staining, Masson staining, echocardiography, myocardial enzyme profiles, and cardiac troponin, and detected the expression of inflammatory factors and antioxidant factors with Western blotting. Immunofluorescence was used to detect the expression of the macrophage marker F4/80.
RESULTS: Our results showed that damage to the heart occurred in the acute and reactivation groups. Impaired cardiac function manifested as a decrease in heart rate and a compensatory increase in left ventricular systolic function. Serum levels of cardiac enzymes also increased dramatically. In the chronic phase, myocardial fibrosis developed, diastolic functions became severely impaired, inflammation persisted, and macrophage expression was slightly reduced. Ultimately, reactivation infection exacerbated damage to cardiac function in mice, potentially leading to diastolic heart failure. Macrophages were strongly activated, and myocardial fibrosis was increased. In addition, the antioxidant capacity of the heart was severely affected by the infection.
CONCLUSIONS: Taken together, these results suggested that the reactivation of T. gondii infection could aggravate injury to the heart, which could be associated with a host-cell-mediated immune response and strong cytokine production by macrophages, thus representing a novel insight into the pathogenic mechanism of toxoplasmosis.