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

Author:

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

Abstract

AbstractCharacterizing 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.

Funder

Deutsche Forschungsgemeinschaft

Joachim Herz Stiftung

Jürgen Manchot Stiftung

Leibniz Centre Infection

Publisher

Springer Science and Business Media LLC

Subject

Multidisciplinary

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