Abstract
BackgroundIn general, immune effector molecules are induced by infection.Methodology and Principal FindingsHowever, 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 IFNγ. Constitutive and IFNγ-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 SignificanceThe role of constitutive hepatocyte expression of Irga6 in resistance to parasites invading from the gut via the hepatic portal system is discussed.
Highlights
Immune resistance genes show low rates of constitutive transcription, and rely on signals generated via infection for their transcriptional induction
The role of constitutive hepatocyte expression of Irga6 in resistance to parasites invading from the gut via the hepatic portal system is discussed
We show here that endogenous Irga6, constitutively expressed in hepatocytes, is able to accumulate on the parasitophorous vacuole membrane of infecting ME49 strain T. gondii, but is ineffective in initiating the vacuolar rupture typical of complex IFNc-induced responses in which multiple immunity-related GTPase (IRG) proteins are expressed at high levels [11,12,13,14]
Summary
Immune resistance genes show low rates of constitutive transcription, and rely on signals generated via infection for their transcriptional induction. The most powerful mediator of elevated transcription of resistance genes is interferon (IFN) c, secreted early in the response to pathogens by natural killer (NK) and NKT cells and later by T helper 1 (Th1) and cytotoxic T cells (TC1) of the adaptive immune system [1]. The immunity-related GTPase (IRG) family of GTPases, responsible for cell-autonomous immunity against a variety of intracellular pathogens [2,3], has seemed to be no exception to this generalization. In our own report of the identification of several IRG proteins [4] we documented strong induction of these proteins in the liver 24 hours after infection with the strongly immunostimulatory pathogen, Listeria monocytogenes, and showed that this induction critically depended on the presence of the IFNc-receptor.
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