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Human guanylate binding proteins potentiate the anti-chlamydia effects of interferon-gamma

Illya Tietzel1, Christelle El-Haibi, Rey A Carabeo

  • 1Department of Natural Sciences, Southern University of New Orleans, New Orleans, LA, USA.

Plos One
|August 5, 2009
PubMed

Insights

Human guanylate binding proteins (hGBPs) 1 and 2 enhance the anti-chlamydial effects of interferon-gamma (IFN-gamma). These hGBPs potentiate IFN-gamma

Area of Science:

  • Immunology
  • Microbiology
  • Cell Biology

Background:

  • Chlamydiae are obligate intracellular bacteria sensitive to interferon-gamma (IFN-gamma).
  • Murine p47 GTPases mediate resistance to chlamydia, but human homologues are unknown, leaving the relevance to human pathogenesis unclear.

Purpose of the Study:

  • To identify and characterize human IFN-gamma-inducible proteins that influence chlamydia infection.
  • To investigate the role of human guanylate binding proteins (hGBPs) 1 and 2 in potentiating IFN-gamma's anti-chlamydial activity.

Main Methods:

  • Localization studies of hGBP1 and hGBP2 within infected cells.
  • Assessment of anti-chlamydial activity of hGBPs alone and in combination with IFN-gamma.
  • Analysis of chlamydia growth upon depletion of hGBP1 and hGBP2 in IFN-gamma-treated cells.
  • Investigation of the effect of hGBP overexpression on chlamydia strains with a specific cytotoxin gene.

Main Results:

  • hGBP1 and hGBP2 localize to the chlamydial inclusion membrane and require their GTPase domain for function.
  • hGBP1 and hGBP2 exhibit mild but significant anti-chlamydial effects alone, which are potentiated by sub-inhibitory IFN-gamma concentrations.
  • Depletion of hGBP1 and hGBP2 reduces IFN-gamma's anti-chlamydial efficacy, leading to increased chlamydia inclusion size.
  • Chlamydia strains expressing a full-length cytotoxin gene are unaffected by hGBP overexpression.

Conclusions:

  • Human guanylate binding proteins (hGBPs) 1 and 2 are key mediators that potentiate the anti-chlamydial effects of IFN-gamma.
  • hGBPs may represent targets of the chlamydial cytotoxin, which confers resistance to IFN-gamma-mediated inhibition.

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