Yifan Wu (Hamburg / DE), Stephanie Leyk (Hamburg / DE), Hanifeh Torabi (Hamburg / DE), Dr. Katharina Höhn (Hamburg / DE), Barbara Honecker (Hamburg / DE), Maria del Pilar Martinez Tauler (Hamburg / DE), Dr. Dániel Cadar (Hamburg / DE), Dr Thomas Jacobs (Hamburg / DE), Prof. Dr. Iris Bruchhaus (Hamburg / DE), Dr. Nahla Galal Metwally (Hamburg / DE)
Abstract text
Plasmodium falciparum is known to cause severe complications to the human host due to cytoadhesion of infected erythrocytes (IEs) to host endothelial cells (ECs). In recent years, evidence has accumulated that cytoadhesion is not the only explanation for the complications associated with malaria. Indirect cell-cell communication can occur through secretion of extracellular vesicles (EVs) into the circulation, containing proteins, DNA, mRNA and microRNAs (miRNAs). Secreted EVs can be taken up by recipient cells, and EVs miRNAs can alter the gene expression in these cells. EVs derived from IEs are known to contain both parasite proteins and human miRNAs. miRNAs can block mRNA by directing degradation through a protein complex or by destabilization of the messenger. Altered miRNA profiles have been described for many types of infections. The miRNA profiles of human ECs during malaria pathogenesis have not yet been studied. We postulate that dysfunction of ECs may play an important role in the prognosis of severe malaria complications. Certain miRNA candidates might control these events by affecting gene expression within the ECs.
Methods: In this study, we investigated if miRNAs play a role in pathogenesis during P. falciparum infection. First, we analysed the miRNA expression profile in the IEs as well as their secreted vesicles using NGS sequencing. Second, we characterised the mRNA and miRNA expression profiles of human brain ECs exposed to co-incubation with P. falciparum IEs.
Results: NGS and bioinformatic analysis showed that 20 miRNA candidates were differentially expressed in the vesicles secreted from the IEs compared to the non-infected ones. In addition, 8 mature microRNA candidates were differentially downregulated in the vesicles secreted from the IEs compared to the non-infected ones. Upon co-incubation of human brain ECs with P. falciparum under low shear stress 8 mature microRNA candidates were differentially expressed.
Conclusion: Our experiments showed that the microRNA profiles of the human erythrocytes and ECs are affected during P. falciparum infection. Mapping these changes might give us more clues about the inflammatory pathways that are turned on during the severe outcomes of the infection.