IFN-γ stimulated murine and human neurons mount anti-parasitic defenses against the intracellular parasite Toxoplasma gondii
Year: 2022
Type: article
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.
Source: Nature Communications
Language: English
Subfield: Parasitology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,890
Funders: U.S. Department of Health and Human Services, National Institutes of Health, BIO5 Institute, University of Arizona, National Institute on Aging, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Neurological Disorders and Stroke
Awards: G2000763682, G2007136651, G2234406165, G2239580460, G2725456623, G3334255353, Defining neuron-Toxoplasma gondii interactions that mediate CNS toxoplasmosis, G3850769870, G5924003189, G6484434974, G6960374846, Infection and Inflammation as Drivers of Aging (IIDA) Predoctoral Training Program, Neuronal Latency and Toxoplasma, G8179016176, G9000216364, University of Arizona's Initiative for Maximizing Student Development (IMSD), Role of ROP16 in Toxoplasma gondii Cyst Development
OpenAlex ID: W4290612166
