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Functional genomic analysis of malaria infection in rhesus macaques.

机译:猕猴疟疾感染的功能基因组分析。

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摘要

This is the first comprehensive investigation of the impact of Plasmodium knowlesi infection on the transcriptome of the peripheral blood mononuclear cells of rhesus macaques. The transcriptome was evaluated at six time points: before infection (the controls), the 4 th day following infection (the liver stage), the 7th, 9th, and 11th days following infection (the blood stage), and four months after curative treatment. The focus of the investigation centered on the evaluation of the innate and acquired immune responses and apoptotic pathways, and the identification of other cellular components which act to limit the progression of the infection. This comprehensive analysis provided important new information regarding host responses utilizing the P. knowlesi-rhesus macaque model. This study provided evidence for a parasite density threshold mechanism associated with the pattern recognition receptors: CD 14 and Toll-like receptors 1, 4, 6, and 8. It was also apparent that apoptosis had a prominent role in defense as indicated by up-regulated components within three different apoptotic pathways: FasL, MAP Kinase and TRAIL. Through this investigation, it was shown that gene expression associated with the defense against malaria does not always increase with the number of days of infection and that many gene expression levels which were significantly up-regulated in the earlier stages of infection decrease to the pre-infection levels as the parasite density increases.
机译:这是首次了解诺氏疟原虫感染对恒河猴猕猴外周血单个核细胞转录组的影响。在六个时间点评估转录组:感染前(对照组),感染后第4天(肝脏阶段),感染后第7天,第9天和第11天(血液阶段)以及治愈后四个月。研究的重点集中在对先天和后天免疫应答和凋亡途径的评估,以及对其他可限制感染进程的细胞成分的鉴定。这项综合分析提供了有关利用知识假单胞菌-猕猴模型对宿主反应的重要新信息。这项研究为与模式识别受体CD 14和Toll样受体1、4、6和8相关的寄生虫密度阈值机制提供了证据。如上图所示,细胞凋亡在防御中也起着重要作用。三种不同的凋亡途径中的调控成分:FasL,MAP激酶和TRAIL。通过这项调查,发现与抗疟疾相关的基因表达并不总是随感染天数的增加而增加,而且在感染早期阶段显着上调的许多基因表达水平下降到感染前。随着寄生虫密度的增加感染水平。

著录项

  • 作者

    Ward, Deborah Williams.;

  • 作者单位

    Howard University.;

  • 授予单位 Howard University.;
  • 学科 Biology Genetics.; Health Sciences Immunology.
  • 学位 Ph.D.
  • 年度 2007
  • 页码 125 p.
  • 总页数 125
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 遗传学;预防医学、卫生学;
  • 关键词

  • 入库时间 2022-08-17 11:39:56

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