Disruption of Toxoplasma gondii Parasitophorous Vacuoles by the Mouse p47-Resistance GTPases

PLoS Pathogens

Gareth Griffiths¹  Sascha Martens²  Iana Parvanova²  Jonathan C Howard²  Gaby Reichmann³  Gudrun Schell³  Jens Zerrahn⁴ 

[1] European Molecular Biology Laboratory, Heidelberg, Germany;Institute for Genetics, University of Cologne, Cologne, Germany;Institute for Medical Microbiology, Heinrich Heine University Duesseldorf, Duesseldorf, Germany;Max Planck Institute for Infection Biology, Berlin, Germany

关键词: Toxoplasma gondii;    Guanosine triphosphatase;    Vacuoles;    Astrocytes;    Parasitic diseases;    Cell membranes;    Immune serum;    Cell staining;   

DOI  :  10.1371/journal.ppat.0010024

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

The p47 GTPases are essential for interferon-γ-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-γ-mediated killing of intracellular parasites. Targeted deletion of the IIGP1 gene results in partial loss of the IFN-γ-mediated T. gondii growth restriction in mouse astrocytes.

【 授权许可】

CC BY