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PLoS Pathog. 2005 Nov;1(3):e24. Epub 2005 Nov 18.

Disruption of Toxoplasma gondii parasitophorous vacuoles by the mouse p47-resistance GTPases.

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  • 1Institute for Genetics, University of Cologne, Cologne, Germany.

Abstract

The p47 GTPases are essential for interferon-gamma-induced cell-autonomous immunity against the protozoan parasite, Toxoplasma gondii, in mice, but the mechanism of resistance is poorly understood. We show that the p47 GTPases, including IIGP1, accumulate at vacuoles containing T. gondii. The accumulation is GTP-dependent and requires live parasites. Vacuolar IIGP1 accumulations undergo a maturation-like process accompanied by vesiculation of the parasitophorous vacuole membrane. This culminates in disruption of the parasitophorous vacuole and finally of the parasite itself. Over-expression of IIGP1 leads to accelerated vacuolar disruption whereas a dominant negative form of IIGP1 interferes with interferon-gamma-mediated killing of intracellular parasites. Targeted deletion of the IIGP1 gene results in partial loss of the IFN-gamma-mediated T. gondii growth restriction in mouse astrocytes.

PMID:
16304607
[PubMed - indexed for MEDLINE]
PMCID:
PMC1287907
Free PMC Article
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