A dedicated promoter drives constitutive expression of the cell-autonomous immune resistance GTPase, Irga6 (IIGP1) in mouse liver

PLoS One. 2009 Aug 26;4(8):e6787. doi: 10.1371/journal.pone.0006787.

Abstract

Background: In general, immune effector molecules are induced by infection.

Methodology and principal findings: However, strong constitutive expression of the cell-autonomous resistance GTPase, Irga6 (IIGP1), was found in mouse liver, contrasting with previous evidence that expression of this protein is exclusively dependent on induction by IFNgamma. Constitutive and IFNgamma-inducible expression of Irga6 in the liver were shown to be dependent on transcription initiated from two independent untranslated 5' exons, which splice alternatively into the long exon encoding the full-length protein sequence. Irga6 is expressed constitutively in freshly isolated hepatocytes and is competent in these cells to accumulate on the parasitophorous vacuole membrane of infecting Toxoplasma gondii tachyzoites.

Conclusions and significance: The role of constitutive hepatocyte expression of Irga6 in resistance to parasites invading from the gut via the hepatic portal system is discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions / genetics
  • Animals
  • Base Sequence
  • Cell Line
  • Exons / genetics
  • GTP Phosphohydrolases / genetics*
  • GTP Phosphohydrolases / immunology
  • GTP Phosphohydrolases / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / genetics*
  • Immunity, Innate / drug effects
  • Immunity, Innate / genetics*
  • Immunity, Innate / immunology
  • Interferon-gamma / immunology
  • Interferon-gamma / pharmacology
  • Introns / genetics
  • Liver / cytology
  • Liver / immunology
  • Liver / metabolism*
  • Liver / parasitology
  • Mice
  • Molecular Sequence Data
  • Promoter Regions, Genetic / genetics*
  • Toxoplasma / immunology
  • Toxoplasma / physiology
  • Transcription, Genetic
  • Vacuoles / drug effects
  • Vacuoles / immunology
  • Vacuoles / metabolism
  • Vacuoles / parasitology

Substances

  • 5' Untranslated Regions
  • Interferon-gamma
  • GTP Phosphohydrolases
  • Iigp1 protein, mouse