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

First Author  Chandrasekaran S Year  2022
Journal  Nat Commun Volume  13
Issue  1 Pages  4605
PubMed ID  35941154 Mgi Jnum  J:327605
Mgi Id  MGI:7329432 Doi  10.1038/s41467-022-32225-z
Citation  Chandrasekaran S, et al. (2022) IFN-gamma stimulated murine and human neurons mount anti-parasitic defenses against the intracellular parasite Toxoplasma gondii. Nat Commun 13(1):4605
abstractText  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 ~50% of these T. gondii-invaded neurons no longer harbor parasites. Finally, IFN-gamma stimulated human pluripotent stem cell derived neurons show an ~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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