Identification of Discriminating Metabolic Pathways and Metabolites in Human PBMCs Stimulated by Various Pathogenic Agents.
Identification of Discriminating Metabolic Pathways and Metabolites in Human PBMCs Stimulated by Various Pathogenic Agents.
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DOI：
10.3389/fphys.2018.00139
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发表时间：
2018
影响因子：
4
通讯作者：
Groen AK
中科院分区：
文献类型：
--
作者：
Zhang X;Mardinoglu A;Joosten LAB;Kuivenhoven JA;Li Y;Netea MG;Groen AK
免疫和细胞代谢是紧密相连的，但目前尚不清楚不同的病原体是否会引起特定的代谢反应。为了解决这个问题，我们研究了差异代谢调节的健康志愿者的外周血单个核细胞（PBMC）的挑战白色念珠菌，伯氏疏螺旋体，脂多糖，结核分枝杆菌在体外。通过整合健康个体受刺激PBMC的基因表达数据与KEGG途径，我们确定了共同的和病原体特异性调节途径，这取决于孵育时间。在4小时的孵育，病原体抑制参与糖酵解和氧化磷酸化途径的基因的表达。相比之下，在24小时的孵育，特别是糖酵解增强，而参与氧化磷酸化的基因在PBMC中保持不变。一般而言，与孵育24小时相比，差异基因表达在4小时不太明显。KEGG途径分析允许念珠菌和细菌刺激诱导的效果之间的差异。基因组规模代谢模型的应用进一步产生了一组103种报告代谢物（例如，链固醇），其可能用作区分念珠菌刺激的PBMC与细菌刺激的PBMC的生物标志物。我们的分析还确定了一组49种代谢物，可以区分伯氏疏螺旋体、脂多糖和结核分枝杆菌的作用。我们的结论是，通过结合KEGG途径和基因组规模的代谢模型分析病原体对PBMC的诱导作用，提供了对与宿主防御相关的代谢变化的深入了解。
Immunity and cellular metabolism are tightly interconnected but it is not clear whether different pathogens elicit specific metabolic responses. To address this issue, we studied differential metabolic regulation in peripheral blood mononuclear cells (PBMCs) of healthy volunteers challenged by Candida albicans, Borrelia burgdorferi, lipopolysaccharide, and Mycobacterium tuberculosis in vitro. By integrating gene expression data of stimulated PBMCs of healthy individuals with the KEGG pathways, we identified both common and pathogen-specific regulated pathways depending on the time of incubation. At 4 h of incubation, pathogenic agents inhibited expression of genes involved in both the glycolysis and oxidative phosphorylation pathways. In contrast, at 24 h of incubation, particularly glycolysis was enhanced while genes involved in oxidative phosphorylation remained unaltered in the PBMCs. In general, differential gene expression was less pronounced at 4 h compared to 24 h of incubation. KEGG pathway analysis allowed differentiation between effects induced by Candida and bacterial stimuli. Application of genome-scale metabolic model further generated a Candida-specific set of 103 reporter metabolites (e.g., desmosterol) that might serve as biomarkers discriminating Candida-stimulated PBMCs from bacteria-stimuated PBMCs. Our analysis also identified a set of 49 metabolites that allowed discrimination between the effects of Borrelia burgdorferi, lipopolysaccharide and Mycobacterium tuberculosis. We conclude that analysis of pathogen-induced effects on PBMCs by a combination of KEGG pathways and genome-scale metabolic model provides deep insight in the metabolic changes coupled to host defense.
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基因集富集分析变得简单。
影响因子：
2.3
作者：
Irizarry RA;Wang C;Zhou Y;Speed TP
通讯作者：
Speed TP
影响因子：
14.9
作者：
Kanehisa M;Goto S;Sato Y;Furumichi M;Tanabe M
通讯作者：
Tanabe M
影响因子：
46.9
作者：
通讯作者：
--
影响因子：
28.3
作者：
Lachmandas, Ekta;Boutens, Lily;Stienstra, Rinke
通讯作者：
Stienstra, Rinke
通过替代变量分析捕获基因表达研究中的异质性。
影响因子：
4.5
作者：
Leek, Jeffrey T.;Storey, John D.
通讯作者：
Storey, John D.