In Astrocytes the Accumulation of the Immunity-Related GTPases Irga6 and Irgb6 at the Vacuole ofToxoplasma gondiiIs Dependent on the Parasite Virulence
Toxoplasma gondiiis an obligate intracellular protozoan parasite responsible for a common infection of the central nervous system. Interferon (IFN)γis the key cytokine of host defence againstT. gondii. However,T. gondiistrains differ in virulence andT. gondiifactors determining virulence are still poorly understood. In astrocytes IFNγprimarily induces immunity-related GTPases (IRGs), providing a cell-autonomous resistance system. Here, we demonstrate that astrocytes prestimulated with IFNγinhibit the proliferation of various avirulent, but not virulent,T. gondiistrains. The two analyzed immunity-related GTPases Irga6 and Irgb6 accumulate at the PV only of avirulentT. gondiistrains, whereas in virulent strains this accumulation is only detectable at very low levels. Both IRG proteins could temporarily be found at the same PV, but did only partially colocalize. Coinfection of avirulent and virulent parasites confirmed that the accumulation of the two analyzed IRGs was a characteristic of the individual PV and not determined by the presence of other strains ofT. gondiiin the same host cell. Thus, in astrocytes the accumulation of Irga6 and Irgb6 significantly differs between avirulent and virulentT. gondiistrains correlating with the toxoplasmacidal properties suggesting a role for this process in parasite virulence.