Adhesion between P. falciparum infected erythrocytes and human endothelial receptors follows alternative binding dynamics under flow and febrile conditions

• Published in: Scientific reports 2020-03, Vol.10 (1), p.4548-4548, Article 4548
• Main Authors: Lubiana, Pedro, Bouws, Philip, Roth, Lisa Katharina, Dörpinghaus, Michael, Rehn, Torben, Brehmer, Jana, Wichers, Jan Stephan, Bachmann, Anna, Höhn, Katharina, Roeder, Thomas, Thye, Thorsten, Gutsmann, Thomas, Burmester, Thorsten, Bruchhaus, Iris, Metwally, Nahla Galal
• Format: Article
• Language: English
• Subjects: 631/326/417/1716; 631/326/417/2547; Adhesion; Bioinformatics; Bronchi - metabolism; Bronchi - parasitology; CD36 antigen; CD36 Antigens - metabolism; CD9 antigen; Cell Adhesion; Cells, Cultured; Endothelial cells; Endothelium, Vascular - metabolism; Endothelium, Vascular - parasitology; Erythrocytes; Erythrocytes - metabolism; Erythrocytes - parasitology; Fever; Humanities and Social Sciences; Humans; Intercellular adhesion molecule 1; Intercellular Adhesion Molecule-1 - metabolism; Malaria; Malaria, Falciparum - metabolism; Malaria, Falciparum - parasitology; multidisciplinary; P-selectin; P-Selectin - metabolism; Parasites; Plasmodium falciparum; Plasmodium falciparum - isolation & purification; Plasmodium falciparum - metabolism; Receptors, Cell Surface - metabolism; Science; Science (multidisciplinary); Vector-borne diseases
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-61388-2

Characterizing the adhesive dynamics of Plasmodium falciparum infected erythrocytes (IEs) to different endothelial cell receptors (ECRs) in flow is a big challenge considering available methods. This study investigated the adhesive dynamics of IEs to five ECRs (CD36, ICAM-1, P-selectin, CD9, CSA) using simulations of in vivo -like flow and febrile conditions. To characterize the interactions between ECRs and knobby and knobless IEs of two laboratory-adapted P. falciplarum isolates, cytoadhesion analysis over time was performed using a new tracking bioinformatics method. The results revealed that IEs performed rolling adhesion exclusively over CD36, but exhibited stationary binding to the other four ECRs. The absence of knobs affected rolling adhesion both with respect to the distance travelled by IEs and their velocity. Knobs played a critical role at febrile temperatures by stabilizing the binding interaction. Our results clearly underline the complexity of the IE-receptor interaction and the importance of knobs for the survival of the parasite at fever temperatures, and lead us to propose a new hypothesis that could open up new strategies for the treatment of malaria.