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Biomarkers of inflammation, immunosuppression and stress with active disease are revealed by metabolomic profiling of tuberculosis patients
Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany.
Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany.
Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany.
Department of Biomedical Sciences, University of Stellenbosch, Cape Town, South Africa.
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2012 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 7, p. e40221-, article id e40221Article in journal (Refereed) Published
Abstract [en]

Although tuberculosis (TB) causes more deaths than any other pathogen, most infected individuals harbor the pathogen without signs of disease. We explored the metabolome of >400 small molecules in serum of uninfected individuals, latently infected healthy individuals and patients with active TB. We identified changes in amino acid, lipid and nucleotide metabolism pathways, providing evidence for anti-inflammatory metabolomic changes in TB. Metabolic profiles indicate increased activity of indoleamine 2,3 dioxygenase 1 (IDO1), decreased phospholipase activity, increased abundance of adenosine metabolism products, as well as indicators of fibrotic lesions in active disease as compared to latent infection. Consistent with our predictions, we experimentally demonstrate TB-induced IDO1 activity. Furthermore, we demonstrate a link between metabolic profiles and cytokine signaling. Finally, we show that 20 metabolites are sufficient for robust discrimination of TB patients from healthy individuals. Our results provide specific insights into the biology of TB and pave the way for the rational development of metabolic biomarkers for TB.

Place, publisher, year, edition, pages
San Fransisco, USA: Public Library Science , 2012. Vol. 7, no 7, p. e40221-, article id e40221
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Bioinformatics and Systems Biology
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URN: urn:nbn:se:oru:diva-40617DOI: 10.1371/journal.pone.0040221ISI: 000306687700009PubMedID: 22844400Scopus ID: 2-s2.0-84864612118OAI: oai:DiVA.org:oru-40617DiVA, id: diva2:777940
Available from: 2015-01-09 Created: 2015-01-09 Last updated: 2018-08-27Bibliographically approved

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CiteExportLink to record
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