Endothelial Cells Potentiate Interferon-gamma Production in a Novel Tripartite Culture Model of Human Cerebral Malaria
Loke Tim Khaw, Helen J Ball, Jacob Golenser, Valery Combes, Georges E Grau, Julie Wheway, Andrew J Mitchell, Nicholas H Hunt
PLoS One | PUBLIC LIBRARY SCIENCE | Published : 2013
We have established a novel in vitro co-culture system of human brain endothelial cells (HBEC), Plasmodium falciparum parasitised red blood cells (iRBC) and peripheral blood mononuclear cells (PBMC), in order to simulate the chief pathophysiological lesion in cerebral malaria (CM). This approach has revealed a previously unsuspected pro-inflammatory role of the endothelial cell through potentiating the production of interferon (IFN)-γ by PBMC and concurrent reduction of interleukin (IL)-10. The IFN-γ increased the expression of CXCL10 and intercellular adhesion molecule (ICAM)-1, both of which have been shown to be crucial in the pathogenesis of CM. There was a shift in the ratio of IL-10:IF..View full abstract
This work was supported by a grant from the National Health and Medical Research Council of Australia to NH and a Sir Zelman Cowen Universities Fund grant to JG and NH. LTK was supported by a scholarship from the Ministry of Science, Technology and Innovation, Malaysia. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.