title: Disruption of Toxoplasma gondii parasitophorous vacuoles by the mouse p47-resistance GTPases.
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.
authors.affiliation: Institute for Genetics, University of Cologne, Cologne, Germany.
authors.forename: Sascha
authors.initials: S
authors.lastname: Martens
authors.forename: Iana
authors.initials: I
authors.lastname: Parvanova
authors.forename: Jens
authors.initials: J
authors.lastname: Zerrahn
authors.forename: Gareth
authors.initials: G
authors.lastname: Griffiths
authors.forename: Gudrun
authors.initials: G
authors.lastname: Schell
authors.forename: Gaby
authors.initials: G
authors.lastname: Reichmann
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Howard
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000469:parasitology; D002478:Cells, Cultured; D020558:GTP Phosphohydrolases / Q000502:physiology*; D006790:Host-Parasite Interactions; D006801:Humans; D007113:Immunity, Innate; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014122:Toxoplasma / Q000378:metabolism*; D014617:Vacuoles / Q000378:metabolism* / Q000469:parasitology
chemical_list: D020558:GTP Phosphohydrolases; C491070:Iigp1 protein, mouse