Role of CD44 protein expressed by syncytiotrophoblast cells in the pathogenesis of malaria during pregnancy
Owino, Simon Odera
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Pregnant women continue to suffer from serious complication due to malaria, particularly worse in first time pregnancies. Susceptibility to infection is due to Plasmodium falciaprum phenotype that expressing adhesive protein VAR2CSA able to interact with placental chondroitin sulfate A (CSA) on fetal cells, syncytiotrophoblast (ST). The resulting sequestration of infected red blood cells (iRBC) in the intervillous space is associated with placental malaria pathology, marked by accumulation of inflammatory cells and damage of the ST. While it is know that ST-adherent iRBC stimulate immune activation of ST, it is yet unclear and remains necessary to determine the signaling molecule on ST as well as the synergistic role other cells, such as monocytes play in mediating immune response. In this study, we explored these question using primary trophoblast cells, a placental choricarcinoma cell line and a monocytic cell line. Here we determined the role of proteoglycan molecule, CD44 in promoting binding of ST-adherent iRBC and the downstream stimulatory of ST via Src kinase family of proteins. Also, we determined role of Toll-like receptor 2 (TLR-2) in monocyte cells and ST cell stimulation, marked by secretion of interleukine-8 (IL-8) cytokine and determined that iRBC profoundly affect the immune activation of these cells, addatively on ST and negatively on monocytes Taken together, these results suggest that during placental malaria, CD44 plays an important receptor and stimulation function on ST by providing CSA ligand for ST-adheren iRBCs and that the ST stimulation is to some degree orchestrated by Src kinases. Also, monocytes and ST cells TLR-2 response is differentially influenced by iRBCs, positively and negatively for ST and monocytes respectively.