Identification of discriminating metabolic pathways and metabolites in human PBMCs stimulated by various pathogenic agents
Journal article, 2018

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.

Peripheral blood mononuclear cell

Candida albicans

Genome scale metabolic model

Lipopolysaccharides

Mycobacterium tuberculosis

Borrelia burgdorferi

Innate immunity

Metabolism

Author

Xiang Zhang

University of Amsterdam

Adil Mardinoglu

Royal Institute of Technology (KTH)

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Leo A.B. Joosten

Radboud University

Jan A. Kuivenhoven

University of Groningen

Yang Li

University of Groningen

Mihai G. Netea

University of Bonn

Radboud University

A. K. Groen

University of Groningen

University of Amsterdam

Frontiers in Physiology

1664-042X (ISSN)

Vol. 9 FEB 139

Subject Categories

Microbiology

Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

Bioinformatics and Systems Biology

DOI

10.3389/fphys.2018.00139

More information

Latest update

4/4/2018 8