Surface Co-Expression of Two Different PfEMP1 Antigens on Single Plasmodium falciparum-Infected Erythrocytes Facilitates Binding to ICAM1 and PECAM1

PLoS Pathogens

Michala E. Victor¹  David E. Arnot¹  Sanne S. Berger¹  Louise Turner¹  Thomas Lavstsen¹  Louise Joergensen¹  Michael B. Dalgaard¹  Dominique C. Bengtsson¹  Thor G. Theander¹  Gerald K. K. Cham¹  Elena Ronander¹  Anja Bengtsson¹  Anja T. R. Jensen² 

[1] Centre for Medical Parasitology, Department of International Health, Immunology & Microbiology, Faculty of Health Sciences, University of Copenhagen and Department of Infectious Diseases, Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark;Institute of Infection and Immunology Research, School of Biology, University of Edinburgh, Edinburgh, Scotland, United Kingdom

关键词: Immune serum;    Flow cytometry;    Red blood cells;    Enzyme-linked immunoassays;    Parasitic diseases;    Cloning;    Confocal microscopy;    Messenger RNA;   

DOI  :  10.1371/journal.ppat.1001083

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

The Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) antigens play a major role in cytoadhesion of infected erythrocytes (IE), antigenic variation, and immunity to malaria. The current consensus on control of variant surface antigen expression is that only one PfEMP1 encoded by one var gene is expressed per cell at a time. We measured var mRNA transcript levels by real-time Q-PCR, analysed var gene transcripts by single-cell FISH and directly compared these with PfEMP1 antigen surface expression and cytoadhesion in three different antibody-selected P. falciparum 3D7 sub-lines using live confocal microscopy, flow cytometry and in vitro adhesion assays. We found that one selected parasite sub-line simultaneously expressed two different var genes as surface antigens, on single IE. Importantly, and of physiological relevance to adhesion and malaria pathogenesis, this parasite sub-line was found to bind both CD31/PECAM1 and CD54/ICAM1 and to adhere twice as efficiently to human endothelial cells, compared to infected cells having only one PfEMP1 variant on the surface. These new results on PfEMP1 antigen expression indicate that a re-evaluation of the molecular mechanisms involved in P. falciparum adhesion and of the accepted paradigm of absolutely mutually exclusive var gene transcription is required.

【 授权许可】

CC BY