TY - JOUR
T1 - Endothelial Cells Potentiate Interferon-γ Production in a Novel Tripartite Culture Model of Human Cerebral Malaria
AU - Khaw, Loke Tim
AU - Ball, Helen J.
AU - Golenser, Jacob
AU - Combes, Valery
AU - Grau, Georges E.
AU - Wheway, Julie
AU - Mitchell, Andrew J.
AU - Hunt, Nicholas H.
PY - 2013/7/12
Y1 - 2013/7/12
N2 - 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:IFN-γ protein from >1 to <1 in the presence of HBEC, associated with the pro-inflammatory process in this model. For this to occur, a direct contact between PBMC and HBEC, but not PBMC and iRBC, was necessary. These results support HBEC playing an active role in the pathogenesis of CM. Thus, if these findings reflect the pathogenesis of CM, inhibition of HBEC and PBMC interactions might reduce the occurrence, or improve the prognosis, of the condition.
AB - 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:IFN-γ protein from >1 to <1 in the presence of HBEC, associated with the pro-inflammatory process in this model. For this to occur, a direct contact between PBMC and HBEC, but not PBMC and iRBC, was necessary. These results support HBEC playing an active role in the pathogenesis of CM. Thus, if these findings reflect the pathogenesis of CM, inhibition of HBEC and PBMC interactions might reduce the occurrence, or improve the prognosis, of the condition.
UR - http://www.scopus.com/inward/record.url?scp=84880068881&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0069521
DO - 10.1371/journal.pone.0069521
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AN - SCOPUS:84880068881
SN - 1932-6203
VL - 8
JO - PLoS ONE
JF - PLoS ONE
IS - 7
M1 - e69521
ER -