Plasmodium falciparum Adhesion on Human Brain Microvascular Endothelial Cells Involves Transmigration-Like Cup Formation and Induces Opening of Intercellular Junctions

PLoS Pathogens

Georges E. Grau¹  Valery Combes²  Pierre-Olivier Couraud³  Ronan Jambou⁴  Babeth B. Weksler⁴  Marie-Jose Jambou⁴ 

[1] Cornell University Medical College, New York, New York, United States of America;Department of Parasitology Mycology, Institut Pasteur, Paris, France;Institut Cochin, CNRS UMR 8104, INSERM U567, Université Paris Descartes, Paris, France;Vascular Immunology Unit, Department of Pathology and Bosch Institute, Sydney Medical School, The University of Sydney, New South Wales, Australia

关键词: Malaria;    White blood cells;    Cerebral malaria;    Red blood cells;    Endothelial cells;    Cell membranes;    Fluorescence microscopy;    Plasmodium;   

DOI  :  10.1371/journal.ppat.1001021

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Cerebral malaria, a major cause of death during malaria infection, is characterised by the sequestration of infected red blood cells (IRBC) in brain microvessels. Most of the molecules implicated in the adhesion of IRBC on endothelial cells (EC) are already described; however, the structure of the IRBC/EC junction and the impact of this adhesion on the EC are poorly understood. We analysed this interaction using human brain microvascular EC monolayers co-cultured with IRBC. Our study demonstrates the transfer of material from the IRBC to the brain EC plasma membrane in a trogocytosis-like process, followed by a TNF-enhanced IRBC engulfing process. Upon IRBC/EC binding, parasite antigens are transferred to early endosomes in the EC, in a cytoskeleton-dependent process. This is associated with the opening of the intercellular junctions. The transfer of IRBC antigens can thus transform EC into a target for the immune response and contribute to the profound EC alterations, including peri-vascular oedema, associated with cerebral malaria.

【 授权许可】

CC BY