Crilly Nathan P, Zita Marcelle Dina, Beaver Alexander K, Sysa-Shah Polina, Bhalodia Aashik, Gabrielson Kathy, Adamo Luigi, Mugnier Monica R
Department of Molecular and Comparative Pathobiology, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
bioRxiv. 2024 Jun 17:2023.10.05.560950. doi: 10.1101/2023.10.05.560950.
is a protozoan parasite that causes human and animal African trypanosomiases (HAT and AAT). Cardiac symptoms are commonly reported in HAT patients, and intracardiac parasites with accompanying myocarditis have been observed in both natural hosts and animal models of infection. Despite the importance of as a cause of cardiac dysfunction and the dramatic socioeconomic impact of African trypanosomiases in sub-Saharan Africa, there are currently no reproducible murine models of -associated cardiomyopathy. We present the first clinically relevant, reproducible murine model of cardiac dysfunction in chronic infection. Similar to humans, mice showed histological evidence of myocarditis and elevation of serum NT-proBNP with electrocardiographic abnormalities. Serum NT-proBNP levels were elevated prior to the development of severe ventricular dysfunction. On flow cytometry, myocarditis was associated with an increase of most myocardial immune cell populations, including multiple T cell and macrophage subsets, corroborating the notion that -associated cardiac damage is an immune-mediated event. This novel mouse model represents a powerful and practical tool to investigate the pathogenesis of -mediated heart damage and supports the development of therapeutic options for -associated cardiac disease.
是一种原生动物寄生虫，可导致人类和动物非洲锥虫病（人类非洲锥虫病和动物非洲锥虫病）。心脏症状在人类非洲锥虫病患者中普遍有报道，并且在自然宿主和感染动物模型中均观察到心脏内寄生虫伴有心肌炎。尽管作为心脏功能障碍的病因以及非洲锥虫病在撒哈拉以南非洲地区造成的巨大社会经济影响具有重要意义，但目前尚无与相关心肌病的可重复小鼠模型。我们展示了首个在慢性感染中与心脏功能障碍相关的具有临床相关性、可重复的小鼠模型。与人类相似，小鼠表现出心肌炎的组织学证据以及血清N末端B型利钠肽原升高且伴有心电图异常。在严重心室功能障碍出现之前，血清N末端B型利钠肽原水平就已升高。通过流式细胞术检测，心肌炎与大多数心肌免疫细胞群体的增加有关，包括多个T细胞和巨噬细胞亚群，这证实了相关心脏损伤是免疫介导事件的观点。这种新型小鼠模型是研究介导的心脏损伤发病机制的强大而实用的工具，并为相关心脏疾病治疗方案的开发提供了支持。
