Transcriptome Analysis of Mouse Brain Infected with Toxoplasma gondii
Transcriptome Analysis of Mouse Brain Infected with Toxoplasma gondii
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DOI：
10.1128/iai.00439-13
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发表时间：
2013-10-01
影响因子：
3.1
通讯作者：
Nishikawa, Yoshifumi
中科院分区：
文献类型：
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作者：
Tanaka, Sachi;Nishimura, Maki;Nishikawa, Yoshifumi
弓形虫是一种专性细胞内寄生虫，可侵入多种脊椎动物宿主细胞。弓形虫的慢性感染在中枢神经系统组织中建立，寄生虫可以直接或间接调节神经元功能。然而，寄生虫引起的大脑神经元疾病的机制仍不清楚。这项研究评估了感染弓形虫后小鼠大脑中宿主基因的表达。 BALB/c小鼠感染PLK毒株，感染32天后，发现额叶的组织病理学病变比大脑其他区域更严重。使用 RNA 测序 (RNA-seq) 对从感染和未感染的小鼠大脑样本中提取的总 RNA 进行转录组分析。在感染弓形虫的小鼠中，935 个小鼠大脑基因上调，而 12 个基因下调。 GOstat分析预测上调的基因主要参与宿主免疫反应和细胞激活。研究发现，受感染小鼠大脑中的寄生虫数量与宿主免疫反应相关基因的表达水平呈正相关。相反，与寄生虫数量呈负相关的基因预计与神经功能有关，例如小 GTP 酶介导的信号转导和囊泡介导的运输。此外，在表现出弓形体病临床症状的小鼠和没有表现出弓形体病临床症状的小鼠之间观察到基因表达差异。我们的研究结果可能有助于了解弓形虫感染期间神经系统变化的机制。
Toxoplasma gondii is an obligate intracellular parasite that invades a wide range of vertebrate host cells. Chronic infections with T. gondii become established in the tissues of the central nervous system, where the parasites may directly or indirectly modulate neuronal function. However, the mechanisms underlying parasite-induced neuronal disorder in the brain remain unclear. This study evaluated host gene expression in mouse brain following infection with T. gondii. BALB/c mice were infected with the PLK strain, and after 32 days of infection, histopathological lesions in the frontal lobe were found to be more severe than in other areas of the brain. Total RNA extracted from infected and uninfected mouse brain samples was subjected to transcriptome analysis using RNA sequencing (RNA-seq). In the T. gondii-infected mice, 935 mouse brain genes were upregulated, whereas 12 genes were downregulated. GOstat analysis predicted that the upregulated genes were primarily involved in host immune responses and cell activation. Positive correlations were found between the numbers of parasites in the infected mouse brains and the expression levels of genes involved in host immune responses. In contrast, genes that had a negative correlation with parasite numbers were predicted to be involved in neurological functions, such as small-GTPase-mediated signal transduction and vesicle-mediated transport. Furthermore, differential gene expression was observed between mice exhibiting the clinical signs of toxoplasmosis and those that did not. Our findings may provide insights into the mechanisms underlying neurological changes during T. gondii infection.