Differential metabolic host response to pathogens associated with community-acquired pneumonia

Ilona den Hartog , Naama Karu , Laura B. Zwep , G. Paul Voorn , Ewoudt M.W. van de Garde , Thomas Hankemeier , J.G. Coen van Hasselt
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Abstract

Background

Metabolic changes induced by the host immune response to pathogens found in patients with community-acquired pneumonia (CAP) may provide insight into its pathogenesis. In this study, we characterized differences in the host metabolic response to common CAP-associated pathogens.

Method

Targeted metabolomic profiling was performed on serum samples obtained from hospitalized CAP patients (n = 119) at admission. We quantified 347 unique metabolites across multiple biochemical classes, including amines, acylcarnitines, and signaling lipids. We evaluated if unique associations between metabolite levels and specific CAP-associated pathogens could be identified.

Results

Several acylcarnitines were found to be elevated in C. burnetii and herpes simplex virus and lowered in M. pneumoniae as compared to other pathogens. Phenylalanine and kynurenine were found elevated in L. pneumophila as compared to other pathogens. S-methylcysteine was elevated in patients with M. pneumoniae, and these patients also showed lowered cortisol levels in comparison to almost all other pathogens. For the herpes simplex virus, we observed a unique elevation of eicosanoids and several amines. Many lysophosphatidylcholines showed an altered profile in C. burnetii versus S. pneumoniae, L. pneumophila, and respiratory syncytial virus. Finally, phosphatidylcholines were negatively affected by the influenza virus in comparison to S. pneumoniae.

Conclusions

In this exploratory analysis, metabolites from different biochemical classes were found to be altered in serum samples from patients with different CAP-associated pathogens, which may be used for hypothesis generation in studies on differences in pathogen host response and pathogenesis of CAP.

不同代谢宿主对社区获得性肺炎相关病原体的反应
背景宿主对社区获得性肺炎(CAP)患者病原体的免疫反应引起的代谢变化可能为其发病机制提供线索。在这项研究中,我们描述了宿主对常见CAP相关病原体代谢反应的差异。方法对住院CAP患者(n=119)入院时的血清样本进行靶向代谢组学分析。我们量化了多种生物化学类别的347种独特代谢物,包括胺、酰基肉毒碱和信号脂质。我们评估了代谢物水平和特定CAP相关病原体之间的独特相关性是否可以确定。结果与其他病原体相比,烧伤杆菌和单纯疱疹病毒中的一些酰基肉毒碱升高,肺炎支原体中的酰基肉毒素降低。与其他病原体相比,嗜肺乳杆菌中的苯丙氨酸和犬尿氨酸含量升高。肺炎支原体患者的S-甲基半胱氨酸升高,与几乎所有其他病原体相比,这些患者的皮质醇水平也降低。对于单纯疱疹病毒,我们观察到类二十烷和几种胺的独特升高。与肺炎链球菌、嗜肺链球菌和呼吸道合胞病毒相比,许多溶血磷脂酰胆碱在burnetii中表现出变化。最后,与肺炎链球菌相比,磷脂酰胆碱受到流感病毒的负面影响。结论在本次探索性分析中,发现不同CAP相关病原体患者血清样本中不同生化类别的代谢产物发生了改变,这可用于研究CAP病原体-宿主反应差异和发病机制的假设生成。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Metabolism open
Metabolism open Agricultural and Biological Sciences (General), Endocrinology, Endocrinology, Diabetes and Metabolism
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