Integrated cytokine and metabolic analysis of pathological responses to parasite exposure in rodents.
Integrated cytokine and metabolic analysis of pathological responses to parasite exposure in rodents.
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DOI：
10.1021/pr901019z
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发表时间：
2010-05-07
影响因子：
4.4
通讯作者：
Holmes, Elaine
中科院分区：
文献类型：
--
作者：
Saric, Jasmina;Li, Jia V.;Swann, Jonathan R.;Utzinger, Juerg;Calvert, Gail;Nicholson, Jeremy K.;Dirnhofer, Stephan;Dallman, Maggie J.;Bictash, Magda;Holmes, Elaine
关键词：
寄生虫感染在哺乳动物宿主中引起免疫和代谢水平上的无数反应。对四种寄生虫-啮齿类动物模型（即伯氏疟原虫小鼠、布氏锥虫小鼠、曼氏血吸虫小鼠和肝片吸虫小鼠）的细胞因子和代谢物进行统计学共分析。1H NMR波谱和多元统计分析对感染和未感染动物的尿液和血浆代谢物谱进行了表征。每一种寄生虫在宿主体内产生一种独特的代谢特征。使用“Meso Scale Discovery”多细胞因子检测平台获得血浆细胞因子浓度。随后使用多变量数据整合方法来阐明与炎症相关的代谢特征成分，并确定与寄生虫诱导的血浆细胞因子水平变化的特定代谢相关性。例如，从伯氏单胞杆菌感染小鼠的血浆代谢物中提取的乙酰糖蛋白的相对水平与IFN-γ具有统计学相关性，而同一细胞因子与葡萄糖水平呈负相关。代谢和细胞因子数据在为联合小鼠数据构建的主成分分析得分图中显示出相似的空间分布，所有感染动物的样本根据寄生虫种类聚类，其中原生动物感染（伯氏弓形虫和布鲁氏弓形虫）与蠕虫感染（曼氏弓形虫）分开分组。mansoni的感染反应细胞因子主要为IL-4和IL-5，与乳酸、胆碱和d-3-羟基丁酸盐共变。本研究表明，对单细胞和多细胞寄生虫的固有差异免疫反应不仅表现在细胞因子的表达上，而且也因此印记在代谢特征上，需要深入分析，进一步探索免疫特征与生化途径之间的直接联系。寄生虫感染在其哺乳动物宿主中引起无数反应，包括一系列免疫反应和代谢紊乱。本研究对四种寄生虫-啮齿类动物模型（即伯氏疟原虫小鼠、布氏锥虫小鼠、曼氏血吸虫小鼠和肝片吸虫小鼠）的细胞因子和代谢物进行了统计共分析。采用1H NMR波谱和多元统计分析对感染和未感染对照动物的尿液和血浆代谢物谱进行了表征。
Parasitic infections cause a myriad of responses in their mammalian hosts, on immune as well as on metabolic level. A multiplex panel of cytokines and metabolites derived from four parasite-rodent models, namely, Plasmodium berghei−mouse, Trypanosoma brucei brucei−mouse, Schistosoma mansoni−mouse, and Fasciola hepatica−rat were statistically coanalyzed. 1H NMR spectroscopy and multivariate statistical analysis were used to characterize the urine and plasma metabolite profiles in infected and noninfected animals. Each parasite generated a unique metabolic signature in the host. Plasma cytokine concentrations were obtained using the ‘Meso Scale Discovery’ multi cytokine assay platform. Multivariate data integration methods were subsequently used to elucidate the component of the metabolic signature which is associated with inflammation and to determine specific metabolic correlates with parasite-induced changes in plasma cytokine levels. For example, the relative levels of acetyl glycoproteins extracted from the plasma metabolite profile in the P. berghei-infected mice were statistically correlated with IFN-γ, whereas the same cytokine was anticorrelated with glucose levels. Both the metabolic and the cytokine data showed a similar spatial distribution in principal component analysis scores plots constructed for the combined murine data, with samples from all infected animals clustering according to the parasite species and whereby the protozoan infections (P. berghei and T. b. brucei) grouped separately from the helminth infection (S. mansoni). For S. mansoni, the main infection-responsive cytokines were IL-4 and IL-5, which covaried with lactate, choline, and d-3-hydroxybutyrate. This study demonstrates that the inherently differential immune response to single- and multicellular parasites not only manifests in the cytokine expression, but also consequently imprints on the metabolic signature, and calls for in-depth analysis to further explore direct links between immune features and biochemical pathways. Parasitic infections cause a myriad of responses in their mammalian hosts, including a range of immune reactions and metabolic perturbations. Here, a multiplex panel of cytokines and metabolites derived from four parasite-rodent models, namely, Plasmodium berghei−mouse, Trypanosoma brucei brucei−mouse, Schistosoma mansoni−mouse, and Fasciola hepatica−rat were statistically coanalyzed. 1H NMR spectroscopy and multivariate statistical analysis were used to characterize the urine and plasma metabolite profiles in infected and noninfected control animals.
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