CD8(+) T cells induce RIPK1-regulated brain endothelial cell death in cerebral malaria.

In mouse cerebral malaria, CD8+ T cells trigger RIPK1-regulated death of brain endothelial cells, and RIPK1 phosphorylation is increased in brain endothelium in human cerebral malaria.

• Why it matters: Immune-driven endothelial injury is central to cerebral malaria, but how cytotoxic T-cell activity translates into blood-brain barrier damage is not well defined.
• What they did: The study combined MRI, 3D tissue-cleared imaging, cross-species pathology, endothelial translatomics, immunocerebrovascular interactomics, and genetic association testing, plus in vitro and in vivo RIPK1 and caspase inhibition.
• The result: RIPK1 kinase inactivation in brain endothelium or systemic RIPK1 pharmacological inhibition prolonged survival in mouse cerebral malaria without changing parasitemia, supporting RIPK1 inhibition as a therapeutic approach.

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