Coordinated loading of IRG resistance GTPases on to the Toxoplasma gondii parasitophorous vacuole.

摘要: Summary The immunity-related GTPases (IRGs) constitute an interferon-induced intracellular resistance mechanism in mice against Toxoplasma gondii. IRG proteins accumulate on the parasitophorous vacuole membrane (PVM), leading to its disruption and death of parasite. How IRGs target PVM is unknown. We show that accumulation begins minutes after parasite invasion increases for about 1 h. Targeting occurs independently several signalling path- ways microtubule network, suggesting transport diffusion-driven. intensity PVM, however, reduced absence autophagy regulator, Atg5. In wild-type cells cooperatively PVMs a definite order reflecting temporal hierarchy, with Irgb6 Irgb10 appar- ently acting as pioneers. Loading onto vacuoles virulent strains attenuated two pioneer are most affected. polymorphic rhoptry kinases, ROP16, ROP18 catalytically inactive proteins, ROP5A-D, not individually responsible this effect. Thus protect avirulent but fail strains. complex cooperative behav- iour resisting may hint at undiscovered complexity also virulence mechanisms.