Plasmodium falciparum and TNF-α Differentially Regulate Inflammatory and Barrier Integrity Pathways in Human Brain Endothelial Cells
Marisol Zuniga, Cláudia Gomes, Ze Chen, Criseyda Martinez, Joseph C. Devlin, P’ng Loke, Ana Rodrı́guez
Abstract
Cerebral malaria is a severe complication of Plasmodium falciparum infection that causes the loss of blood-brain barrier integrity and frequently results in death. Here, we compared the effect of P. falciparum-infected red blood cells and inflammatory cytokines, like TNF-α, in the loss of BBB integrity. We observed that while TNF-α induced a small increase in barrier permeability, P. falciparum-infected red blood cells led to a severe loss of barrier integrity. Our results establish that there are fundamental differences in the responses induced by TNF-α and P. falciparum on brain endothelial cells and suggest that parasite-induced signaling is a major component driving the disruption of the BBB during cerebral malaria, proposing a potential target for much needed therapeutics.