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Genome-Wide Expression Profiling in Malaria Infection Reveals Transcriptional Changes Associated with Lethal and Nonlethal Outcomes

机译:疟疾感染的全基因组表达谱揭示了与致死和非致死结果相关的转录变化。

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High-density oligonucleotide microarrays are widely used to study gene expression in cells exposed to a variety of pathogens. This study addressed the global genome-wide transcriptional activation of genes in hosts infected in vivo, which result in radically different clinical outcomes. We present an analysis of the gene expression profiles that identified a set of host biomarkers which distinguish between lethal and nonlethal blood stage Plasmodium yoelii malaria infections. Multiple biological replicates sampled during the course of infection were used to establish statistically valid sets of differentially expressed genes. These genes that correlated with the intensity of infection were used to identify pathways of cellular processes related to metabolic perturbations, erythropoiesis, and B-cell immune responses and other innate and cellular immune responses. The transcriptional apparatus that controls gene expression in erythropoiesis was also differentially expressed and regulated the expression of target genes involved in the host's response to malaria anemia. The biological systems approach provides unprecedented opportunities to explore the pathophysiology of host-pathogen interactions in experimental malaria infection and to decipher functionally complex networks of gene and protein interactions.
机译:高密度寡核苷酸微阵列被广泛用于研究暴露于多种病原体的细胞中的基因表达。这项研究解决了体内感染宿主的基因在全球基因组范围内的转录激活,这导致了完全不同的临床结果。我们对基因表达谱进行了分析,鉴定了一组宿主生物标志物,这些标志物区分了致死性和非致死性血友病疟原虫感染。在感染过程中取样的多个生物学重复样本用于建立统计有效的差异表达基因集。这些与感染强度相关的基因被用于鉴定与代谢扰动,红细胞生成和B细胞免疫反应以及其他先天和细胞免疫反应有关的细胞过程的途径。控制红细胞生成中基因表达的转录装置也被差异表达并调节参与宿主对疟疾贫血反应的靶基因的表达。生物系统方法为探索实验性疟疾感染中宿主与病原体相互作用的病理生理学和破译功能复杂的基因和蛋白质相互作用网络提供了前所未有的机会。

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