CD8+ T cells and human cerebral malaria: a shifting episteme
Laurent Rénia, … , Georges E.R. Grau, Samuel C. Wassmer
Laurent Rénia, … , Georges E.R. Grau, Samuel C. Wassmer
Published February 17, 2020
Citation Information: J Clin Invest. 2020;130(3):1109-1111. https://doi.org/10.1172/JCI135510.
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Commentary

CD8+ T cells and human cerebral malaria: a shifting episteme

Abstract

Mosquito-transmitted Plasmodium falciparum infection can cause human cerebral malaria (HCM) with high mortality rates. The abundance of infected red blood cells that accumulate in the cerebral vasculature of patients has led to the belief that these brain-sequestered cells solely cause pathogenesis. However, animal models suggest that CD8+ T cells migrate to and accumulate in the brain, directly contributing to experimental cerebral malaria (ECM) mortality. In this issue of the JCI, Riggle et al. explored the brain vasculature from 34 children who died from HCM or other causes and frequently found CD3+ CD8+ T cells in contact with endothelial cells. Further, the authors show that coinfection with HIV enhanced such CD3+ CD8+ T cell luminal distribution. These findings suggest that the mouse model for cerebral malaria may accurately reflect human disease pathology. This study sheds new light on the mechanisms behind blood-brain barrier breakdown in this complicated neurological disease and opens up alternative approaches for treatment.

Authors

Laurent Rénia, Georges E.R. Grau, Samuel C. Wassmer

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Figure 1

Proposed chain of events contributing to the blood-brain barrier breakdown in HCM.

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Proposed chain of events contributing to the blood-brain barrier breakdo...
P. falciparum–parasitized red blood cells can transfer parasite antigens to the surface of brain microvascular endothelial cells either by direct contact (22) (i), or through the production of antigen-carrying extracellular vesicles that can potentially bind the endothelial surface (ii). P. falciparum antigens are then picked up and presented by the endothelial cells through their class I MHC (23) (iii). Cytotoxic T lymphocytes (CTL) engage with antigen-presenting endothelial cells via their TCR and CD8 receptors (iv), leading to the release of granzyme B by CTL (13) (v), the apoptosis of targeted endothelial cells (18) (vi), and an alteration of the blood-brain barrier, ultimately resulting in vasogenic edema (17) (vii).