Caspase-8 expression in CD8 ⁺ T cells promotes pathogen restriction in the brain during <i>Toxoplasma gondii</i> infection

Cell death is an integral restriction mechanism against intracellular pathogens. We have previously reported extensive cell death in the brain during infection with the intracellular parasite, <i>Toxoplasma gondii.</i> Here, we focus on the role of caspase-8, a regulator of extrinsic apoptosis, during <i>T. gondii</i> infection. We find that <i>Casp8^-/-Ripk3^-/-</i> mice have increased brain parasite burden in comparison to controls and succumb to infection despite the generation of robust immune responses. We observed that neurons, astrocytes, and CD8⁺ T cells had high rates of parasite interactions in <i>Casp8^-/-Ripk3^-/-</i> mice compared to wild-type mice. While <i>Casp8</i> deficiency in neurons and astrocytes did not affect control of infection, deletion of <i>Casp8</i> in CD8⁺ T cells led to impaired survival, increased parasite burden, and direct infection of CD8⁺ T cells in the brain. We conclude that in addition to well-characterized effector functions, CD8⁺ T cells use caspase-8 to control <i>T. gondii</i> in the brain.