Genomewide analysis of the host response to malaria in Kenyan children

Genomewide analysis of the host response to malaria in Kenyan children
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DOI:
10.1086/429297
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发表时间:
2005-05-15
影响因子:
6.4
通讯作者:
Kwiatkowski, DP
Kwiatkowski, DP
中科院分区:
医学2区
文献类型:
--
作者:
Griffiths, MJ;Shafi, MJ;Kwiatkowski, DP

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疟疾是一个全球性问题,迫切需要进一步了解这一疾病过程。当疟疾寄生虫在血液中入侵和发展时,它们会激发宿主的深刻反应,其主要临床症状是发烧。为了探索这种反应,我们测量了患有急性疟疾或其他发热性疾病住院的肯尼亚儿童全血中宿主基因的表达。全基因组表达分析确定了与中性粒细胞和红系活性相关的两个主要基因表达谱。除了这些一般的急性反应外,第三个基因表达谱与宿主寄生虫血症有关;红细胞吞噬和细胞应激的介质是这种反应的显著组成部分。根据基因表达模式对受试者的描述提供了宿主对疟疾反应的分子视角,并进一步从功能上洞察了发病的潜在过程。
Malaria is a global problem, and there is a critical need for further understanding of the disease process. When malarial parasites invade and develop within the bloodstream, they stimulate a profound host response whose main clinical sign is fever. To explore this response, we measured host gene expression in whole blood from Kenyan children hospitalized with either acute malaria or other febrile illnesses. Genomewide analysis of expression identified 2 principal gene-expression profiles related to neutrophil and erythroid activity. In addition to these general acute responses, a third gene-expression profile was associated with host parasitemia; mediators of erythrophagocytosis and cellular stress were notable components of this response. The delineation of subjects on the basis of patterns of gene expression provides a molecular perspective of the host response to malaria and further functional insight into the underlying processes of pathogenesis.