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先天性弓形虫病小鼠模型的建立及用于评估母体和胎儿组织中寄生虫载量的定量聚合酶链反应检测方法的验证

Establishment of a murine model of congenital toxoplasmosis and validation of a qPCR assay to assess the parasite load in maternal and fetal tissues.

作者信息

Souza Jéssica S, Farani Priscila S G, Ferreira Beatriz I S, Barbosa Helene S, Menna-Barreto Rubem F S, Moreira Otacilio C, Mariante Rafael M

机构信息

Laboratório de Biologia Estrutural, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil.

Plataforma de PCR em Tempo Real RPT09A, Laboratório de Virologia Molecular, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil.

出版信息

Front Microbiol. 2023 Feb 27;14:1124378. doi: 10.3389/fmicb.2023.1124378. eCollection 2023.

Abstract

is the causative agent of toxoplasmosis, a disease that affects warm-blooded animals and one third of the human population worldwide. Pregnant women who have never been exposed to the parasite constitute an important risk group, as infection during pregnancy often leads to congenital toxoplasmosis, the most severe form of the disease. Current therapy for toxoplasmosis is the same as it was 50 years ago and has little or no effect when vertical transmission occurs. Therefore, it is urgent to develop new strategies to prevent mother-to-fetus transmission. The implementation of experimental animal models of congenital toxoplasmosis that reproduces the transmission rates and clinical signs in humans opens an avenue of possibilities to interfere in the progression of the disease. In addition, knowing the parasite load in maternal and fetal tissues after infection, which may be related to organ abnormalities and disease outcome, is another important step in designing a promising intervention strategy. Therefore, we implemented here a murine model of congenital toxoplasmosis with outbred Swiss Webster mice infected intravenously with tachyzoites of the ME49 strain of that mimics the frequency of transmission of the parasite, as well as important clinical signs of human congenital toxoplasmosis, such as macrocephaly, in addition to providing a highly sensitive quantitative real-time PCR assay to assess parasite load in mouse tissues. As the disease is not restricted to humans, also affecting several domestic animals, including companion animals and livestock, they can also benefit from the model presented in this study.

摘要

是弓形虫病的病原体,这种疾病影响温血动物以及全球三分之一的人口。从未接触过该寄生虫的孕妇构成一个重要的风险群体,因为孕期感染通常会导致先天性弓形虫病,这是该疾病最严重的形式。目前治疗弓形虫病的方法与50年前相同,当发生垂直传播时几乎没有效果。因此,迫切需要制定新的策略来预防母婴传播。建立能够重现人类传播率和临床症状的先天性弓形虫病实验动物模型,为干预疾病进展开辟了一条可能的途径。此外,了解感染后母体和胎儿组织中的寄生虫载量,这可能与器官异常和疾病结局有关,是设计有前景的干预策略的另一个重要步骤。因此,我们在此采用了一种先天性弓形虫病小鼠模型,用远交系瑞士韦伯斯特小鼠静脉注射该ME49株速殖子,该模型模拟了寄生虫的传播频率,以及人类先天性弓形虫病的重要临床症状,如巨头畸形,此外还提供了一种高度灵敏的定量实时PCR检测方法来评估小鼠组织中的寄生虫载量。由于该疾病不仅限于人类,还影响包括伴侣动物和家畜在内的几种家畜,它们也可以从本研究中提出的模型中受益。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3595/10009190/6c4d1005b88c/fmicb-14-1124378-g001.jpg

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