Transcriptomic Profiling of Mouse Brain During Acute and Chronic Infections by Toxoplasma gondii Oocysts.

Transcriptomic Profiling of Mouse Brain During Acute and Chronic Infections by Toxoplasma gondii Oocysts.
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弓形虫卵囊急性和慢性感染期间小鼠大脑的转录组分析

DOI:
10.3389/fmicb.2020.570903
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发表时间:
2020
影响因子:
5.2
通讯作者:
Cong W
Cong W
中科院分区:
生物学2区
文献类型:
--
作者:
Hu RS;He JJ;Elsheikha HM;Zou Y;Ehsan M;Ma QN;Zhu XQ;Cong W

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原生动物弓形虫的感染会对感染者的大脑结构和功能产生毁灭性的影响,特别是免疫功能受损的患者。脑转录组的系统生物学观点可以确定介导脑弓形虫病神经发病机制的关键分子靶点和途径。在这里,我们使用RNA测序(RNA-seq)对感染了Pru株弓形虫卵囊的小鼠在感染后11天和33天(Dpi)与未感染(对照)小鼠的大脑进行了转录转录分析。弓形虫分别在11dpi和33dpi改变了936和2081个转录本的表达,其中大部分在感染的大脑中上调。基因本体论(GO)浓缩和通径分析表明,免疫应答,如干扰素-γ应答基因,在11dpi受到强烈影响。同样,与T细胞激活、细胞因子产生和免疫细胞增殖相关的差异表达转录本(DET)在33dpi时显著改变。宿主-寄生虫相互作用组分析表明,一些DET参与了免疫信号、代谢、生物合成相关过程和种间相互作用。这些发现应该会增加对小鼠大脑转录组的了解,以及在急性和慢性弓形虫感染过程中转录调控和下游信号通路的变化。
Infection by the protozoan Toxoplasma gondii can have a devastating impact on the structure and function of the brain of the infected individuals, particularly immunocompromised patients. A systems biology view of the brain transcriptome can identify key molecular targets and pathways that mediate the neuropathogenesis of cerebral toxoplasmosis. Here, we performed transcriptomic analysis of the brain of mice infected by T. gondii Pru strain oocysts at 11 and 33 days post-infection (dpi) compared to uninfected (control) mice using RNA sequencing (RNA-seq). T. gondii altered the expression of 936 and 2,081 transcripts at 11 and 33 dpi, respectively, and most of these were upregulated in the infected brains. Gene Ontology (GO) enrichment and pathway analysis showed that immune response, such as interferon-gamma (IFN-γ) responsive genes were strongly affected at 11dpi. Likewise, differentially expressed transcripts (DETs) related to T cell activation, cytokine production and immune cell proliferation were significantly altered at 33 dpi. Host-parasite interactome analysis showed that some DETs were involved in immune signaling, metabolism, biosynthesis-related processes and interspecies interaction. These findings should increase knowledge of the mouse brain transcriptome and the changes in transcriptional regulation and downstream signaling pathways during acute and chronic T. gondii infections.
DOI: 10.1371/journal.ppat.1005643
发表时间: 2016-06
期刊: PLoS pathogens
影响因子: 6.7
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David CN;Frias ES;Szu JI;Vieira PA;Hubbard JA;Lovelace J;Michael M;Worth D;McGovern KE;Ethell IM;Stanley BG;Korzus E;Fiacco TA;Binder DK;Wilson EH
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影响因子: 3.3
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