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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Biomarkers of inflammation, immunosuppression and stress with active disease are revealed by metabolomic profiling of tuberculosis patients
PLoS ONE, Volume 7, No. 7, Article e40221, Year 2012
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Description
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. © 2012 Weiner et al.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3402490/bin/pone.0040221.s001.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC3402490/bin/pone.0040221.s002.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC3402490/bin/pone.0040221.s003.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC3402490/bin/pone.0040221.s004.docx
https://efashare.b-cdn.net/share/pmc/articles/PMC3402490/bin/pone.0040221.s005.docx
https://efashare.b-cdn.net/share/pmc/articles/PMC3402490/bin/pone.0040221.s006.docx
https://efashare.b-cdn.net/share/pmc/articles/PMC3402490/bin/pone.0040221.s007.docx
Authors & Co-Authors
Weiner, January Mikolaj
Germany, Berlin
Max Planck Institute for Infection Biology
Parida, Shreemanta K.
Germany, Berlin
Max Planck Institute for Infection Biology
India, New Delhi
Ministry of Science and Technology, India
Maertzdorf, Jeroen
Germany, Berlin
Max Planck Institute for Infection Biology
Black, Gillian Frances
South Africa, Stellenbosch
Stellenbosch University
South Africa, Cape Town
Sustainable Livelihoods Foundation
Repsilber, Dirk
Germany, Dummerstorf
Research Institute for Farm Animal Biology Fbn
Telaar, Anna
Germany, Dummerstorf
Research Institute for Farm Animal Biology Fbn
Mohney, Robert P.
United States, Morrisville
Metabolon, Inc.
Arndt-Sullivan, Cordelia
Germany, Berlin
Max Planck Institute for Infection Biology
Germany, Berlin
Humboldt-universität zu Berlin
Ganoza, Christian A.
Germany, Berlin
Max Planck Institute for Infection Biology
Faé, Kellen Cristhina
Germany, Berlin
Max Planck Institute for Infection Biology
Walzl, Gerhard
South Africa, Stellenbosch
Stellenbosch University
Kaufmann, Stefan Hugo Ernst
Germany, Berlin
Max Planck Institute for Infection Biology
Statistics
Citations: 141
Authors: 12
Affiliations: 7
Identifiers
Doi:
10.1371/journal.pone.0040221
e-ISSN:
19326203
Research Areas
Infectious Diseases
Noncommunicable Diseases