Marinho Claudio R F, Bucci Daniella Z, Dagli Maria Lúcia Z, Bastos Karina R B, Grisotto Marcos G, Sardinha Luiz R, Baptista Cristiane R G M, Gonçalves Carlos Penha, Lima Maria Regina D'Império, Alvarez José M
Department of Immunology, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, São Paulo, Brazil.
Infect Immun. 2004 Apr;72(4):2350-7. doi: 10.1128/IAI.72.4.2350-2357.2004.
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(2) 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.
恰加斯病是由克氏锥虫引起的一种慢性感染性疾病，是拉丁美洲一项重要的公共卫生负担。该病通常在数十年内难以察觉地发展，而在相当一部分受影响个体中，最终会因心力衰竭而死亡。在此，我们描述了一种使用从一名人类患者（西尔维奥X10/4）分离出的稳定克隆建立的新型克氏锥虫慢性感染小鼠模型。C3H/HePAS小鼠品系中的感染呈慢性进展，主要特征是出现强烈的心脏炎性病变，这重现了人类疾病中观察到的慢性心脏病理变化。C3H/HePAS小鼠中也存在中度横纹肌病变。在C3H/HePAS小鼠的慢性心脏病变中检测到并回收了活的寄生虫，这支持了目前关于恰加斯病心脏病理发展与寄生虫在炎症组织中持续存在有关的观点。相比之下，在感染的A/J小鼠中，慢性炎性病变主要针对肝脏和骨骼肌，而心脏中未检测到病理变化和寄生虫。对F1（A/J×C3H/HePAS）和F2（A/J×C3H/HePAS）小鼠的表型分析表明，由克氏锥虫（西尔维奥X10/4克隆）引起的炎性病变的遗传易感性是异质性的，因为心脏和肝脏病理变化在F2代中分离。这些发现提出了一个假说，即恰加斯病患者中观察到的病理异质性（心脏或消化慢性病变的有无）可能归因于宿主遗传因素。
