Tissue-specific responses of brain and lung endothelial cell miRNA and mRNA profiles to the ring-stage Plasmodium falciparum-infected red blood cells

MicroRNAs (miRNAs) control 60% of genes expressed in the human body, but their role in malaria pathogenesis is incompletely understood. For the first time, we demonstrate cell type-specific alterations to the miRNA profiles during the early response to malaria infection in brain and lung endothelial cells (ECs). In brain ECs, incubation with Plasmodium falciparum -infected red blood cells in the ring stage (iRBCs) most significantly affected endocytosis-related miRNAs and mRNAs. Contrastingly, in lung ECs, iRBCs altered electron transport chain-related miRNAs and mRNAs. We also present a novel dataset of inherent differences between microRNA profiles in brain and lung ECs and their secreted extracellular vesicles (EVs). We demonstrated that shear stress affected multiple pathways in brain ECs, which were controlled by numerous human miRNAs. Together, these findings demonstrate that host miRNAs respond to parasite exposure; this is accompanied by stimulation of downstream signaling pathways within the ECs. Therefore, we consider miRNAs to be the initial spark (Code of duty) for the early host-parasite interaction events.