Why it might be bad for brain cells to eat malaria parasites

Abstract

In this issue, Adams et al. (2021. J. Exp. Med. https://doi.org/10.1084/jem.20201266) show that red blood cells infected with strains of Plasmodium falciparum, which are commonly found in cerebral malaria patients, are specifically internalized by brain endothelial cells, perhaps contributing to the symptoms of the disease.

Insights from Matthew K. Higgins.

Human erythrocytes infected with the malaria parasite, Plasmodium falciparum, produce adhesive PfEMP1 proteins that allow them to interact with human endothelial receptors. Some of the these PfEMP1 bind to ICAM-1 and some bind to EPCR, while some can simultaneously bind to both ICAM-1 and EPCR. Adams et al. (2021) show that brain endothelial cells can specifically internalize infected erythrocytes that bind to both ICAM-1 and EPCR. This leads to endothelial cell swelling and increased permeability, perhaps contributing to the severe symptoms of cerebral malaria.