Unique gene expression profiles of human macrophages and dendritic cells to phylogenetically distinct parasites
Unique gene expression profiles of human macrophages and dendritic cells to phylogenetically distinct parasites
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DOI：
10.1182/blood-2002-10-3232
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发表时间：
2003-07-15
期刊：
影响因子：
20.3
通讯作者：
Nutman, TB
中科院分区：
文献类型：
--
作者：
Chaussabel, D;Semnani, RT;Nutman, TB
将来自同一个体献血者的体外产生的单核细胞衍生的树突状细胞 (DC) 和巨噬细胞 (Mphis) 暴露于 5 种不同的病原体，并通过微阵列分析评估基因表达谱。研究人员检查了对结核分枝杆菌、系统发育上不同的原生动物（大型利什曼原虫、杜氏利什曼原虫、弓形虫）和蠕虫（马来丝虫）寄生虫的反应，每种寄生虫都会在人类中产生慢性感染，但它们引发的免疫反应的性质差异很大。在没有微生物刺激的情况下，DC 和 Mphi 组成型表达大约 4000 个基因，其中 96% 在两种细胞类型之间共享。相比之下，病原体暴露后 DC 和 Mphi 中的基因转录改变主要是细胞特异性的。对基因表达数据的分析导致在所有测试的实验条件下鉴定出一组紧密共同调控的基因。新设计的基于文献的聚类算法能够识别功能和转录同质的基因组。通过这种策略对各个病原体诱导的反应进行比较，揭示了与每种传染原相关的功能相关基因谱的主要差异。尽管细胞内病原体诱导的反应与细胞外马来亚细亚细菌明显不同，但它们各自都表现出独特的基因表达模式，而这种模式不一定能根据其系统发育关系来预测。特征功能簇与每种传染原的关联与抗原呈递细胞具有预先连接的信号模式以用于响应不同病原体的概念是一致的。 (C) 2003 年，美国血液学会。
Monocyte-derived dendritic cells (DCs) and macrophages (Mphis) generated in vitro from the same individual blood donors were exposed to 5 different pathogens, and gene expression profiles were assessed by microarray analysis. Responses to Mycobacterium tuberculosis and to phylogenetically distinct protozoan (Leishmania major, Leishmania donovani, Toxoplasma gondii) and helminth (Brugia malayi) parasites were examined, each of which produces chronic infections in humans yet vary considerably in the nature of the immune responses they trigger. In the absence of microbial stimulation, DCs and Mphis constitutively expressed approximately 4000 genes, 96% of which were shared between the 2 cell types. In contrast, the genes altered transcriptionally in DCs and Mphis following pathogen exposure were largely cell specific. Profiling of the gene expression data led to the identification of sets of tightly coregulated genes across all experimental conditions tested. A newly devised literature-based clustering algorithm enabled the identification of functionally and transcriptionally homogenous groups of genes. A comparison of the responses induced by the individual pathogens by means of this strategy revealed major differences in the function-ally related gene profiles associated with each infectious agent. Although the intracellular pathogens induced responses clearly distinct from the extracellular B malayi, they each displayed a unique pattern of gene expression that would not necessarily be predicted on the basis of their phylogenetic relationship. The association of characteristic functional clusters with each infectious agent is consistent with the concept that antigen-presenting cells have prewired signaling patterns for use in the response to different pathogens. (C) 2003 by The American Society of Hematology.