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Identification of d...
Identification of discriminating metabolic pathways and metabolites in human PBMCs stimulated by various pathogenic agents
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- Zhang, Xiang (författare)
- Universiteit Van Amsterdam,University of Amsterdam
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- Mardinoglu, Adil, 1982 (författare)
- KTH,Science for Life Laboratory, SciLifeLab,Chalmers University of Technology, Sweden
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- Joosten, Leo A.B. (författare)
- Radboud Universiteit,Radboud University
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- Kuivenhoven, Jan A. (författare)
- Rijksuniversiteit Groningen,University of Groningen
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- Li, Yang (författare)
- Rijksuniversiteit Groningen,University of Groningen
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- Netea, Mihai G. (författare)
- Universität Bonn,University of Bonn,Radboud Universiteit,Radboud University
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- Groen, A. K. (författare)
- Rijksuniversiteit Groningen,University of Groningen,Universiteit Van Amsterdam,University of Amsterdam
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(creator_code:org_t)
- 2018-02-27
- 2018
- Engelska.
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Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 9:FEB
- Relaterad länk:
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https://research.cha... (primary) (free)
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https://www.frontier...
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https://doi.org/10.3...
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https://research.cha...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- NATURVETENSKAP -- Biologi -- Mikrobiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Microbiology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Bioinformatik och systembiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Bioinformatics and Systems Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Physiology (hsv//eng)
Nyckelord
- Peripheral blood mononuclear cell
- Candida albicans
- Genome scale metabolic model
- Lipopolysaccharides
- Mycobacterium tuberculosis
- Borrelia burgdorferi
- Innate immunity
- Metabolism
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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