De Alba-Alvarado Mariana, Bucio-Torres Martha Irene, Zenteno Edgar, Sampedro-Carrillo Enrique, Hernández-Lopez Mariana, Reynoso-Ducoing Olivia, Torres-Gutiérrez Elia, Guevara-Gomez Yolanda, Guerrero-Alquicira Raquel, Cabrera-Bravo Margarita, Salazar-Schettino Paz María
Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico.
Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico.
Front Vet Sci. 2020 Oct 6;7:568745. doi: 10.3389/fvets.2020.568745. eCollection 2020.
Cardiopathy is a common, irreversible manifestation of the chronic phase of Chagas disease; however, there is controversy as to how the causes for progression from the acute to the chronic phase are defined. In this work, the presence of the parasite is correlated with the occurrence of cell infiltration and fibrosis in cardiac tissues, as well as IgG detection and disease progression in a murine model. Fifty CD1 mice were infected intraperitoneally with , while 30 control were administered with saline solution. Parasitemia levels were determined, and IgG titers were quantified by ELISA. At different times, randomly selected mice were euthanized, and the heart was recovered. Cardiac tissue slides were stained with HE and Masson trichrome stain. A significant increase in parasitemia levels was observed after 15 days post-infection (dpi), with a maximum of 4.1 × 10 parasites on 33 dpi, ending on 43 dpi; amastigote nests were observed on 15-62 dpi. Histological analysis revealed lymphocytic infiltration and fibrotic lesions from 8 dpi until the end of the study, on 100 dpi. The presence of plasma cells in the myocardium observed on 40-60 dpi, accompanied by seropositivity to ELISA on 40-100 dpi, was regarded as the hallmark of the transition phase. Meanwhile, the chronic phase, characterized by the absence of amastigotes, presence of cell infiltration, fibrotic lesions, and seropositivity, started on 62 dpi. A strong correlation between parasitemia and the presence of amastigote nests was found ( = 0.930), while correlation between the presence of fibrosis and of amastigote nests was weak ( = 0.306), and that between fibrosis and lymphocyte infiltration on 100 dpi was strong ( = 0.899). The murine model is suitable to study Chagas disease, since it can reproduce the chronic and acute phases of the human disease. The acute phase was determined to occur on 1-60 dpi, while the chronic phase starts on 62 dpi, and fibrotic damage is a consequence of the continuous inflammatory infiltration; on the other hand, fibrosis was determined to start on the acute phase, being more apparent in the chronic phase, when Chagas disease-related cardiopathy is induced.
心脏病是恰加斯病慢性期常见的、不可逆的表现;然而,关于从急性期进展到慢性期的原因如何界定存在争议。在这项研究中,在小鼠模型中,寄生虫的存在与心脏组织中的细胞浸润和纤维化的发生以及IgG检测和疾病进展相关。50只CD1小鼠经腹腔注射感染,而30只对照小鼠给予盐溶液。测定了寄生虫血症水平,并通过ELISA定量IgG滴度。在不同时间,随机选择小鼠实施安乐死,并取出心脏。心脏组织切片用苏木精-伊红(HE)和马松三色染色法染色。感染后15天(dpi)观察到寄生虫血症水平显著升高,在33 dpi时最高达到4.1×10个寄生虫,在43 dpi时结束;在15 - 62 dpi观察到无鞭毛体巢。组织学分析显示,从8 dpi直到研究结束的100 dpi,存在淋巴细胞浸润和纤维化病变。在40 - 60 dpi观察到心肌中有浆细胞存在,同时在40 - 100 dpi ELISA检测呈血清阳性,这被视为过渡阶段的标志。同时,以无无鞭毛体、存在细胞浸润、纤维化病变和血清阳性为特征的慢性期在62 dpi开始。发现寄生虫血症与无鞭毛体巢的存在之间存在强相关性( = 0.930),而纤维化与无鞭毛体巢的存在之间的相关性较弱( = 0.306),并且在100 dpi时纤维化与淋巴细胞浸润之间的相关性较强( = 0.899)。该小鼠模型适合用于研究恰加斯病,因为它可以重现人类疾病的慢性期和急性期。急性期确定为发生在1 - 60 dpi,而慢性期在62 dpi开始,纤维化损伤是持续炎症浸润的结果;另一方面,纤维化确定在急性期开始,在慢性期更明显,此时会诱发与恰加斯病相关的心脏病。