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Identification of Discriminating Metabolic Pathways and Metabolites in Human PBMCs Stimulated by Various Pathogenic Agents
KTH, Centres, Science for Life Laboratory, SciLifeLab. Chalmers University of Technology, Sweden.
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2018 (English)In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 9, article id 139Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2018. Vol. 9, article id 139
Keywords [en]
innate immunity, metabolism, peripheral blood mononuclear cell, Candida albicans, lipopolysaccharides, Mycobacterium tuberculosis, Borrelia burgdorferi, genome scale metabolic model
National Category
Physiology
Identifiers
URN: urn:nbn:se:kth:diva-224696DOI: 10.3389/fphys.2018.00139ISI: 000426217900003Scopus ID: 2-s2.0-85042713175OAI: oai:DiVA.org:kth-224696DiVA, id: diva2:1192749
Funder
Science for Life Laboratory - a national resource center for high-throughput molecular bioscienceEU, FP7, Seventh Framework Programme, FP7 305707
Note

QC 20180323

Available from: 2018-03-23 Created: 2018-03-23 Last updated: 2018-03-23Bibliographically approved

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Mardinoglu, Adil

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