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Biomarkers of Inflammation, Immunosuppression and Stress Are Revealed by Metabolomic Profiling of Tuberculosis Patients
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....
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3402490/ https://www.ncbi.nlm.nih.gov/pubmed/22844400 http://dx.doi.org/10.1371/journal.pone.0040221 |
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author | Weiner, January Parida, Shreemanta K. Maertzdorf, Jeroen Black, Gillian F. Repsilber, Dirk Telaar, Anna Mohney, Robert P. Arndt-Sullivan, Cordelia Ganoza, Christian A. Faé, Kellen C. Walzl, Gerhard Kaufmann, Stefan H. E. |
author_facet | Weiner, January Parida, Shreemanta K. Maertzdorf, Jeroen Black, Gillian F. Repsilber, Dirk Telaar, Anna Mohney, Robert P. Arndt-Sullivan, Cordelia Ganoza, Christian A. Faé, Kellen C. Walzl, Gerhard Kaufmann, Stefan H. E. |
author_sort | Weiner, January |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-3402490 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-34024902012-07-27 Biomarkers of Inflammation, Immunosuppression and Stress Are Revealed by Metabolomic Profiling of Tuberculosis Patients Weiner, January Parida, Shreemanta K. Maertzdorf, Jeroen Black, Gillian F. Repsilber, Dirk Telaar, Anna Mohney, Robert P. Arndt-Sullivan, Cordelia Ganoza, Christian A. Faé, Kellen C. Walzl, Gerhard Kaufmann, Stefan H. E. PLoS One Research Article 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. Public Library of Science 2012-07-23 /pmc/articles/PMC3402490/ /pubmed/22844400 http://dx.doi.org/10.1371/journal.pone.0040221 Text en © 2012 Weiner et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Weiner, January Parida, Shreemanta K. Maertzdorf, Jeroen Black, Gillian F. Repsilber, Dirk Telaar, Anna Mohney, Robert P. Arndt-Sullivan, Cordelia Ganoza, Christian A. Faé, Kellen C. Walzl, Gerhard Kaufmann, Stefan H. E. Biomarkers of Inflammation, Immunosuppression and Stress Are Revealed by Metabolomic Profiling of Tuberculosis Patients |
title | Biomarkers of Inflammation, Immunosuppression and Stress Are Revealed by Metabolomic Profiling of Tuberculosis Patients |
title_full | Biomarkers of Inflammation, Immunosuppression and Stress Are Revealed by Metabolomic Profiling of Tuberculosis Patients |
title_fullStr | Biomarkers of Inflammation, Immunosuppression and Stress Are Revealed by Metabolomic Profiling of Tuberculosis Patients |
title_full_unstemmed | Biomarkers of Inflammation, Immunosuppression and Stress Are Revealed by Metabolomic Profiling of Tuberculosis Patients |
title_short | Biomarkers of Inflammation, Immunosuppression and Stress Are Revealed by Metabolomic Profiling of Tuberculosis Patients |
title_sort | biomarkers of inflammation, immunosuppression and stress are revealed by metabolomic profiling of tuberculosis patients |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3402490/ https://www.ncbi.nlm.nih.gov/pubmed/22844400 http://dx.doi.org/10.1371/journal.pone.0040221 |
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