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Response and recovery in the plasma metabolome tracks the acute LCMV-induced immune response

Academic Article
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Overview

authors

  • Wikoff, W. R.
  • Kalisak, E.
  • Trauger, S.
  • Manchester, Marianne
  • Siuzdak, Gary

publication date

  • July 2009

journal

  • Journal of Proteome Research  Journal

abstract

  • Lymphocytic choriomeningitis virus (LCMV) infection of mice is noncytopathic, producing well-characterized changes reflecting the host immune response. Untargeted metabolomics using mass spectrometry identified endogenous small molecule changes in blood from mice inoculated with LCMV, sampled at days 1, 3, 7, and 14 post infection. These time points correspond to well characterized events during acute LCMV infection and the immune response. Diverse pathways were altered, including TCA cycle intermediates, gamma-glutamyl dipeptides, lysophosphatidyl cholines, and fatty acids. The kynurenine pathway was activated, surprising because it is stimulated by IFN-gamma, which LCMV suppresses, thus, suggesting alternative activators. In contrast, biopterin/neopterin, another IFN-gamma stimulated pathway, was not activated. Many metabolites followed "response and recovery" kinetics, decreasing after infection to a minimum at days 3-7, and returning to normal by day 14. The TCA pathway followed this pattern, including citrate, cis-aconitate and alpha-ketoglutarate, intriguing because succinate has been shown to mediate cellular immunity. This response and recovery dynamic tracks the immune response, including the rise and fall of natural killer cell populations, serum TNF receptor concentration, and viral clearance. Metabolomics can provide target pathways for molecular diagnostics or therapeutics of viral infection and immunity.

subject areas

  • Animals
  • Blood Proteins
  • Immunity, Innate
  • Interferon-gamma
  • Kinetics
  • Lymphocytic choriomeningitis virus
  • Male
  • Mass Spectrometry
  • Metabolome
  • Metabolomics
  • Mice
  • Mice, Inbred C57BL
  • Models, Biological
  • Models, Chemical
  • Systems Biology
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Research

keywords

  • innate immunity
  • mass spectrometry
  • metabolism
  • systems biology
  • untargeted metabolomics
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Identity

PubMed Central ID

  • PMC3437991

International Standard Serial Number (ISSN)

  • 1535-3893

Digital Object Identifier (DOI)

  • 10.1021/pr900275p

PubMed ID

  • 19496611
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Additional Document Info

start page

  • 3578

end page

  • 3587

volume

  • 8

issue

  • 7

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