Host response profile of human brain proteome in toxoplasma encephalitis co-infected with HIV.
Host response profile of human brain proteome in toxoplasma encephalitis co-infected with HIV.
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DOI：
10.1186/1559-0275-11-39
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发表时间：
2014
影响因子：
3.8
通讯作者：
Shankar SK
中科院分区：
文献类型：
--
作者：
Sahu A;Kumar S;Sreenivasamurthy SK;Selvan LD;Madugundu AK;Yelamanchi SD;Puttamallesh VN;Dey G;Anil AK;Srinivasan A;Mukherjee KK;Gowda H;Satishchandra P;Mahadevan A;Pandey A;Prasad TS;Shankar SK
弓形虫脑炎是由机会性原生动物寄生虫弓形虫引起的。免疫功能正常的个体初次感染弓形虫时基本上没有症状。相反，在免疫功能低下的个体中，寄生虫的重新激活会导致严重的并发症和死亡。宿主中枢神经系统中蛋白质水平的分子变化以及与弓形虫脑炎发病机制相关的蛋白质在很大程度上尚未被探索。我们使用全局定量蛋白质组学策略来识别弓形虫感染与 HIV 共感染期间人类宿主中差异调节的蛋白质和受影响的分子网络。当将诊断为弓形虫脑炎的患者的大脑额叶与对照脑组织进行比较时，我们鉴定了 3,496 种蛋白质，其中 607 种蛋白质存在差异表达（≥1.5 倍）。我们通过免疫组织化学验证了3种蛋白的差异表达，证实其与质谱分析一致。差异表达蛋白的通路分析表明，涉及抗原加工、免疫反应、神经元生长、神经递质转运和能量代谢的数条通路失调。本研究采用全局定量蛋白质组学方法，对同时感染艾滋病毒的弓形虫脑炎患者的脑组织进行了比较蛋白质组谱分析。差异表达的蛋白质包括先前报道的以及弓形虫和 HIV 感染背景下的几种新蛋白质，可以进一步研究。确定与该疾病相关的分子途径应该增强我们对弓形虫脑炎发病机制的理解。本文的在线版本 (doi:10.1186/1559-0275-11-39) 包含补充材料，可供授权用户使用。
Toxoplasma encephalitis is caused by the opportunistic protozoan parasite Toxoplasma gondii. Primary infection with T. gondii in immunocompetent individuals remains largely asymptomatic. In contrast, in immunocompromised individuals, reactivation of the parasite results in severe complications and mortality. Molecular changes at the protein level in the host central nervous system and proteins associated with pathogenesis of toxoplasma encephalitis are largely unexplored. We used a global quantitative proteomic strategy to identify differentially regulated proteins and affected molecular networks in the human host during T. gondii infection with HIV co-infection. We identified 3,496 proteins out of which 607 proteins were differentially expressed (≥1.5-fold) when frontal lobe of the brain from patients diagnosed with toxoplasma encephalitis was compared to control brain tissues. We validated differential expression of 3 proteins through immunohistochemistry, which was confirmed to be consistent with mass spectrometry analysis. Pathway analysis of differentially expressed proteins indicated deregulation of several pathways involved in antigen processing, immune response, neuronal growth, neurotransmitter transport and energy metabolism. Global quantitative proteomic approach adopted in this study generated a comparative proteome profile of brain tissues from toxoplasma encephalitis patients co-infected with HIV. Differentially expressed proteins include previously reported and several new proteins in the context of T. gondii and HIV infection, which can be further investigated. Molecular pathways identified to be associated with the disease should enhance our understanding of pathogenesis in toxoplasma encephalitis. The online version of this article (doi:10.1186/1559-0275-11-39) contains supplementary material, which is available to authorized users.
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影响因子：
48
作者：
Andenmatten, Nicole;Egarter, Saskia;Jackson, Allison J;Jullien, Nicolas;Herman, Jean-Paul;Meissner, Markus
通讯作者：
Meissner, Markus
影响因子：
10.5
作者：
Fergusson, David M.;Boden, Joseph M.;Kennedy, Martin A.
通讯作者：
Kennedy, Martin A.
影响因子：
3.7
作者：
Jesse, Sarah;Lehnert, Stefan;Otto, Markus
通讯作者：
Otto, Markus
影响因子：
4.5
作者：
Eastwood, SL;Harrison, PJ
通讯作者：
Harrison, PJ
DOI：
10.1523/jneurosci.1256-12.2012
发表时间：
2012-10-17
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Hamby ME;Coppola G;Ao Y;Geschwind DH;Khakh BS;Sofroniew MV
通讯作者：
Sofroniew MV