Disruption of <em>Toxoplasma gondii</em> Parasitophorous Vacuoles by the Mouse p47-Resistance GTPases

<div><p>The p47 GTPases are essential for interferon-γ-induced cell-autonomous immunity against the protozoan parasite, <em>Toxoplasma gondii,</em> in mice, but the mechanism of resistance is poorly understood. We show that the p47 GTPases, including IIGP1, accumulate at vacuoles containing <em>T. gondii.</em> 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-γ-mediated killing of intracellular parasites. Targeted deletion of the IIGP1 gene results in partial loss of the IFN-γ-mediated <em>T. gondii</em> growth restriction in mouse astrocytes.</p>