IFN-gamma stimulated murine and human neurons mount anti-parasitic defenses against the intracellular parasite Toxoplasma gondii

Dogma holds that Toxoplasma gondii persists in neurons because neurons cannot clear intracellular parasites, even with IFN-gamma stimulation. As several recent studies questioned this idea, here we use primary murine neuronal cultures from wild type and transgenic mice in combination with IFN-gamma stimulation and parental and transgenic parasites to reassess IFN-gamma dependent neuronal clearance of intracellular parasites. We find that neurons respond to IFN-gamma and that a subset of neurons clear intracellular parasites via immunity regulated GTPases. Whole neuron reconstructions from mice infected with parasites that trigger neuron GFP expression only after full invasion reveal that similar to 50% of these T. gondii-invaded neurons no longer harbor parasites. Finally, IFN-gamma stimulated human pluripotent stem cell derived neurons show an similar to 50% decrease in parasite infection rate when compared to unstimulated cultures. This work highlights the capability of human and murine neurons to mount cytokine-dependent anti-T. gondii defense mechanisms in vitro and in vivo.