Yifan Wu (Hamburg / DE), Hanifeh Torabi (Hamburg / DE), Stephan Lorenzen (Hamburg / DE), Prof. Dr. Iris Bruchhaus (Hamburg / DE), Dr. Nahla Galal Metwally (Hamburg / DE)
Abstract text
Introduction:
Sequestration of Plasmodium falciparum in human microvessels occurs due to an interaction between a parasite ligand and host endothelial cell (EC) receptor in a process called cytoadhesion. Cytoadhesion results in microvascular obstruction, impaired perfusion, hypoxia and finally organ failure. PfEMP1 (Plasmodium falciparum erythrocyte membrane protein-1) is encoded by approximately 60 var genes per parasite genome and is considered the most important surface antigen of P. falciparum-infected erythrocytes (IEs).
Objectives:
Characterization of the tropism of PfEMP1 for different EC receptors and the subsequent immune response triggered by cytoadhesion.
Materials & methods:
In this study, we enriched P. falciparum isolates IT4 over resting or TNF-α-activated human brain microvascular endothelial cells (HBMECs). Furthermore, we stimulated HBMECs with enriched parasites for 4 hours and 8 hours separately and characterized the HBMECs transcriptomic changes. Moreover, in order to simulate the in vivo condition we stimulated HBMECs with IEs under defined shear stress. mRNA and miRNA profiles of stimulated HBMECs were characterized by NGS.
Results:
Transcriptome analysis indicated that 101 differentially expressed genes (DEGs) were identified in HBMECs after 4 hours of stimulation and 51 DEGs were identified in HBMECs after 8 hours of stimulation. Reactome analysis of DEGs revealed the enrichment in antigen presentation and interferon gamma signal pathway. Interestingly, we found the mRNA expression level of oligoadenylate synthase (OAS) gene family increased significantly after 4 hours of stimulation.
Conclusion:
By comparing the transcriptomes of HBMECs stimulated for 4 h and 8 h, we observed upregulation of immunoregulatory genes within the first 4 h of stimulation. However, these immune response declines by reaching 8 h of coincubation. Besides, shear stress stimulation may affect the mRNA and miRNA profiles of HBMECs.