Pathology affects different organs in two mouse strains chronically infected by a Trypanosoma cruzi clone:: a model for genetic a studies of Chagas' disease
Pathology affects different organs in two mouse strains chronically infected by a Trypanosoma cruzi clone:: a model for genetic a studies of Chagas' disease
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DOI：
10.1128/iai.72.4.2350-2357.2004
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发表时间：
2004-04-01
影响因子：
3.1
通讯作者：
Alvarez, JM
中科院分区：
文献类型：
--
作者：
Marinho, CRF;Bucci, DZ;Alvarez, JM
恰加斯病是一种由克氏锥虫引起的慢性感染，是拉丁美洲的一个重要公共卫生负担。这种疾病经常在几十年内无法检测到，而在相当一部分受影响的个体中，它最终因心力衰竭而死亡。在这里，我们描述了一种新的小鼠模型的慢性感染T。cruzi使用分离自人类患者的稳定克隆（Sylvio X10/4）。C3 H/HePAS小鼠品系中的感染慢性进展，主要特征为强烈的心脏炎性病变，其重现了在人类疾病中观察到的慢性心脏病理学。C3 H/HePAS小鼠中也存在中度横纹肌病变。从C3 H/HePAS小鼠的慢性心脏病变中检测到并回收了活的寄生虫，这支持了目前的观点，即恰加斯病中心脏病理学的发展与发炎组织中的寄生虫持续存在有关。相比之下，在受感染的A/J小鼠中，慢性炎症病变针对肝脏和骨骼肌，而心脏中的病理和寄生虫是检测不到的。F-1（A/J × C3 H/HePAS）和F-2（A/J × C3 H/HePAS）小鼠的表型分析表明，T. cruzi（Sylvio X10/4克隆）是异质的，因为心脏和肝脏病理在F1代分离。这些发现提出了一个假设，即在恰加斯病患者中观察到的病理学异质性（心脏或消化道慢性病变的存在和不存在）可能归因于宿主遗传因素。
Chagas' disease is a chronic infection caused by Trypanosoma cruzi and represents an important public health burden in Latin America. Frequently the disease evolves undetectable for decades, while in a significant fraction of the affected individuals it culminates in death by heart failure. Here, we describe a novel murine model of the chronic infection with T. cruzi using a stable clone isolated from a human patient (Sylvio X10/4). The infection in the C3H/HePAS mouse strain progresses chronically and is mainly characterized by intense cardiac inflammatory lesions that recapitulate the chronic cardiac pathology observed in the human disease. Moderate striated muscle lesions are also present in C3H/HePAS mice. Viable parasites are detected and recovered from the chronic heart lesions of C3H/HePAS mice, supporting the current notion that development of heart pathology in Chagas' disease is related to parasite persistence in the inflamed tissue. By contrast, in infected A/J mice, chronic inflammatory lesions are targeted to the liver and the skeletal muscle, while pathology and parasites are undetectable in the heart. The phenotypic analysis of F-1 (A/J x C3H/HePAS) and F-2 (A/J x C3H/HePAS) mice suggests that the genetic predisposition to develop the inflammatory lesions caused by T. cruzi (Sylvio X10/4 clone) is heterogeneous because the heart and liver pathology segregate in the F, generation. These findings raise the hypothesis that the pathology heterogeneity observed in humans with Chagas' disease (absence and presence of cardiac or digestive chronic lesions) may be attributable to host genetic factors.