National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido, Japan.
Infect Immun. 2013 Oct;81(10):3609-19. doi: 10.1128/IAI.00439-13. Epub 2013 Jul 15.
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.
刚地弓形虫是一种专性细胞内寄生虫,可入侵广泛的脊椎动物宿主细胞。慢性弓形虫感染会在中枢神经系统的组织中建立,寄生虫可能直接或间接调节神经元功能。然而,寄生虫引起大脑神经元紊乱的机制尚不清楚。本研究评估了弓形虫感染后小鼠大脑中的宿主基因表达。用 PLK 株感染 BALB/c 小鼠,感染 32 天后,发现额叶的组织病理学损伤比大脑其他区域更严重。从感染和未感染的小鼠脑组织样本中提取总 RNA,并用 RNA 测序(RNA-seq)进行转录组分析。在弓形虫感染的小鼠中,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。在感染的小鼠脑中,寄生虫数量与参与宿主免疫反应的基因表达水平之间存在正相关。相比之下,与寄生虫数量呈负相关的基因被预测与神经功能有关,如小 GTPase 介导的信号转导和囊泡介导的运输。此外,还观察到表现出弓形虫病临床症状的小鼠与未表现出临床症状的小鼠之间存在差异基因表达。我们的发现可能为了解弓形虫感染期间神经变化的机制提供了线索。