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bioRxiv · 10.1101/2021.11.10.468098

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

Chandrasekaran, S.·Kochanowsky, J. A.·Merritt, E. F.·Koshy, A. A.
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Abstract

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, we used 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 found 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 revealed that [~]40% of these T. gondii-invaded neurons no longer harbor parasites. Finally, IFN-{gamma} stimulated human stem cell derived neurons showed a [~] 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.

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Chandrasekaran, S., Kochanowsky, J. A., Merritt, E. F., Koshy, A. A.. 2021-11-11. IFN-γ stimulated murine and human neurons mount anti-parasitic defenses against the intracellular parasite Toxoplasma gondii. https://doi.org/10.1101/2021.11.10.468098

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