Surface co-expression of two different PfEMP1 antigens on single plasmodium falciparum-infected erythrocytes facilitates binding to ICAM1 and PECAM1.
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...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2010-09-01
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| Series: | PLoS Pathogens |
| Online Access: | http://europepmc.org/articles/PMC2932717?pdf=render |
| _version_ | 1811212264439545856 |
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| author | Louise Joergensen Dominique C Bengtsson Anja Bengtsson Elena Ronander Sanne S Berger Louise Turner Michael B Dalgaard Gerald K K Cham Michala E Victor Thomas Lavstsen Thor G Theander David E Arnot Anja T R Jensen |
| author_facet | Louise Joergensen Dominique C Bengtsson Anja Bengtsson Elena Ronander Sanne S Berger Louise Turner Michael B Dalgaard Gerald K K Cham Michala E Victor Thomas Lavstsen Thor G Theander David E Arnot Anja T R Jensen |
| author_sort | Louise Joergensen |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T05:26:12Z |
| format | Article |
| id | doaj.art-e7d83cb8e67e4e2ab236dfe6b66642b7 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-04-12T05:26:12Z |
| publishDate | 2010-09-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-e7d83cb8e67e4e2ab236dfe6b66642b72022-12-22T03:46:18ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742010-09-0169e100108310.1371/journal.ppat.1001083Surface co-expression of two different PfEMP1 antigens on single plasmodium falciparum-infected erythrocytes facilitates binding to ICAM1 and PECAM1.Louise JoergensenDominique C BengtssonAnja BengtssonElena RonanderSanne S BergerLouise TurnerMichael B DalgaardGerald K K ChamMichala E VictorThomas LavstsenThor G TheanderDavid E ArnotAnja T R JensenThe 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.http://europepmc.org/articles/PMC2932717?pdf=render |
| spellingShingle | Louise Joergensen Dominique C Bengtsson Anja Bengtsson Elena Ronander Sanne S Berger Louise Turner Michael B Dalgaard Gerald K K Cham Michala E Victor Thomas Lavstsen Thor G Theander David E Arnot Anja T R Jensen Surface co-expression of two different PfEMP1 antigens on single plasmodium falciparum-infected erythrocytes facilitates binding to ICAM1 and PECAM1. PLoS Pathogens |
| title | Surface co-expression of two different PfEMP1 antigens on single plasmodium falciparum-infected erythrocytes facilitates binding to ICAM1 and PECAM1. |
| title_full | Surface co-expression of two different PfEMP1 antigens on single plasmodium falciparum-infected erythrocytes facilitates binding to ICAM1 and PECAM1. |
| title_fullStr | Surface co-expression of two different PfEMP1 antigens on single plasmodium falciparum-infected erythrocytes facilitates binding to ICAM1 and PECAM1. |
| title_full_unstemmed | Surface co-expression of two different PfEMP1 antigens on single plasmodium falciparum-infected erythrocytes facilitates binding to ICAM1 and PECAM1. |
| title_short | Surface co-expression of two different PfEMP1 antigens on single plasmodium falciparum-infected erythrocytes facilitates binding to ICAM1 and PECAM1. |
| title_sort | surface co expression of two different pfemp1 antigens on single plasmodium falciparum infected erythrocytes facilitates binding to icam1 and pecam1 |
| url | http://europepmc.org/articles/PMC2932717?pdf=render |
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