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

Sambamurthy Chandrasekaran, Joshua A. Kochanowsky, Emily F. Merritt, Joseph S. Lagas, Ayesha Swannigan and Anita A. Koshy ()
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Sambamurthy Chandrasekaran: University of Arizona
Joshua A. Kochanowsky: University of Arizona
Emily F. Merritt: University of Arizona
Joseph S. Lagas: University of Arizona
Ayesha Swannigan: University of Arizona
Anita A. Koshy: University of Arizona

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: Abstract Dogma holds that Toxoplasma gondii persists in neurons because neurons cannot clear intracellular parasites, even with IFN-γ 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-γ stimulation and parental and transgenic parasites to reassess IFN-γ dependent neuronal clearance of intracellular parasites. We find that neurons respond to IFN-γ 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-γ 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.

Date: 2022
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DOI: 10.1038/s41467-022-32225-z

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