Expression of sphingosine-1-phosphate receptor 1 in the brain of fatal cerebral malaria

The signaling pathway activated by sphingosine-1-phosphate (S1P) through S1P receptor 1 (S1PR1) plays specific roles in regulating vascular integrity and preventing vascular leakage during inflammatory response. Endothelial cell barrier dysfunction has been implicated in cerebral malaria (CM) pathology. To explore the S1P/S1PR1 signaling pathway in CM, the study investigated the expression of S1PR1 in the brain of fatal malaria and correlated with the level of S1P and malaria severity. Localisation of S1PR1 in brain tissues was evaluated using immunohistochemistry technique in archived brain tissues of fatal P. falciparum malaria. S1P level was determined using enzyme-linked immunosorbent assay (ELISA). S1PR1 expression was intense in cerebral blood vessels and neurons of fatal CM patients compared to brain tissues from control group and non-CM patients (all p < 0.001). S1P level in the blood decreased significantly in CM group and was negatively correlated with S1PR1 expression in blood vessels and neurons. The expression of S1PR1 in cerebral blood vessels and neurons indicates that S1P/S1PR1 signaling pathway is involved in malaria pathogenesis and represents potential targets for S1P/S1PR1 modulators to treat CM. The outcomes can serve as a basis to explore measures to block the expression of S1PR1 which could reduce sequestration.