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Biomarkers of inflammation, immunosuppression and stress with active disease are revealed by metabolomic profiling of tuberculosis patients

Weiner, January, 3rd (författare)
Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany
Parida, Shreemanta K (författare)
Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany
Maertzdorf, Jeroen (författare)
Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany
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Black, Gillian F (författare)
Department of Biomedical Sciences, University of Stellenbosch, Cape Town, South Africa
Repsilber, Dirk, 1971- (författare)
Biomathematics/Bioinformatics Group, Genetics and Biometry, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany
Telaar, Anna (författare)
Biomathematics/Bioinformatics Group, Genetics and Biometry, Leibniz Institute for Farm Animal Biology, FBN, Dummerstorf, Germany
Mohney, Robert P (författare)
Metabolon Inc., Durham NC, USA
Arndt-Sullivan, Cordelia (författare)
Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany
Ganoza, Christian A (författare)
Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany
Faé, Kellen C (författare)
Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany
Walzl, Gerhard (författare)
Department of Biomedical Sciences, University of Stellenbosch, Cape Town, South Africa
Kaufmann, Stefan H E (författare)
Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany
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 (creator_code:org_t)
2012-07-23
2012
Engelska.
Ingår i: PLOS ONE. - San Fransisco, USA : Public Library Science. - 1932-6203. ; 7:7, s. e40221-
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • 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.

Ämnesord

NATURVETENSKAP  -- Biologi -- Bioinformatik och systembiologi (hsv//swe)
NATURAL SCIENCES  -- Biological Sciences -- Bioinformatics and Systems Biology (hsv//eng)

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