Different PfEMP1-expressing Plasmodium falciparum variants induce divergent endothelial transcriptional responses during co-culture.
The human malaria parasite Plasmodium falciparum is responsible for the majority of mortality and morbidity caused by malaria infection and differs from other human malaria species in the degree of accumulation of parasite-infected red blood cells in the microvasculature, known as cytoadherence or s...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2023-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0295053&type=printable |
| _version_ | 1827207820039159808 |
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| author | Basim Othman Leo Zeef Tadge Szestak Zineb Rchiad Janet Storm Caroline Askonas Rohit Satyam Aymen Madkhali Michael Haley Simon Wagstaff Kevin Couper Arnab Pain Alister Craig |
| author_facet | Basim Othman Leo Zeef Tadge Szestak Zineb Rchiad Janet Storm Caroline Askonas Rohit Satyam Aymen Madkhali Michael Haley Simon Wagstaff Kevin Couper Arnab Pain Alister Craig |
| author_sort | Basim Othman |
| collection | DOAJ |
| description | The human malaria parasite Plasmodium falciparum is responsible for the majority of mortality and morbidity caused by malaria infection and differs from other human malaria species in the degree of accumulation of parasite-infected red blood cells in the microvasculature, known as cytoadherence or sequestration. In P. falciparum, cytoadherence is mediated by a protein called PfEMP1 which, due to its exposure to the host immune system, undergoes antigenic variation resulting in the expression of different PfEMP1 variants on the infected erythrocyte membrane. These PfEMP1s contain various combinations of adhesive domains, which allow for the differential engagement of a repertoire of endothelial receptors on the host microvasculature, with specific receptor usage associated with severe disease. We used a co-culture model of cytoadherence incubating human brain microvascular endothelial cells with erythrocytes infected with two parasite lines expressing different PfEMP1s that demonstrate different binding profiles to vascular endothelium. We determined the transcriptional profile of human brain microvascular endothelial cells (HBMEC) following different incubation periods with infected erythrocytes, identifying different transcriptional profiles of pathways previously found to be involved in the pathology of severe malaria, such as inflammation, apoptosis and barrier integrity, induced by the two PfEMP1 variants. |
| first_indexed | 2024-03-08T23:56:17Z |
| format | Article |
| id | doaj.art-eb71af4d90ea4deead6c86fc63501d28 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2025-03-21T12:46:08Z |
| publishDate | 2023-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-eb71af4d90ea4deead6c86fc63501d282024-06-27T05:31:30ZengPublic Library of Science (PLoS)PLoS ONE1932-62032023-01-011811e029505310.1371/journal.pone.0295053Different PfEMP1-expressing Plasmodium falciparum variants induce divergent endothelial transcriptional responses during co-culture.Basim OthmanLeo ZeefTadge SzestakZineb RchiadJanet StormCaroline AskonasRohit SatyamAymen MadkhaliMichael HaleySimon WagstaffKevin CouperArnab PainAlister CraigThe human malaria parasite Plasmodium falciparum is responsible for the majority of mortality and morbidity caused by malaria infection and differs from other human malaria species in the degree of accumulation of parasite-infected red blood cells in the microvasculature, known as cytoadherence or sequestration. In P. falciparum, cytoadherence is mediated by a protein called PfEMP1 which, due to its exposure to the host immune system, undergoes antigenic variation resulting in the expression of different PfEMP1 variants on the infected erythrocyte membrane. These PfEMP1s contain various combinations of adhesive domains, which allow for the differential engagement of a repertoire of endothelial receptors on the host microvasculature, with specific receptor usage associated with severe disease. We used a co-culture model of cytoadherence incubating human brain microvascular endothelial cells with erythrocytes infected with two parasite lines expressing different PfEMP1s that demonstrate different binding profiles to vascular endothelium. We determined the transcriptional profile of human brain microvascular endothelial cells (HBMEC) following different incubation periods with infected erythrocytes, identifying different transcriptional profiles of pathways previously found to be involved in the pathology of severe malaria, such as inflammation, apoptosis and barrier integrity, induced by the two PfEMP1 variants.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0295053&type=printable |
| spellingShingle | Basim Othman Leo Zeef Tadge Szestak Zineb Rchiad Janet Storm Caroline Askonas Rohit Satyam Aymen Madkhali Michael Haley Simon Wagstaff Kevin Couper Arnab Pain Alister Craig Different PfEMP1-expressing Plasmodium falciparum variants induce divergent endothelial transcriptional responses during co-culture. PLoS ONE |
| title | Different PfEMP1-expressing Plasmodium falciparum variants induce divergent endothelial transcriptional responses during co-culture. |
| title_full | Different PfEMP1-expressing Plasmodium falciparum variants induce divergent endothelial transcriptional responses during co-culture. |
| title_fullStr | Different PfEMP1-expressing Plasmodium falciparum variants induce divergent endothelial transcriptional responses during co-culture. |
| title_full_unstemmed | Different PfEMP1-expressing Plasmodium falciparum variants induce divergent endothelial transcriptional responses during co-culture. |
| title_short | Different PfEMP1-expressing Plasmodium falciparum variants induce divergent endothelial transcriptional responses during co-culture. |
| title_sort | different pfemp1 expressing plasmodium falciparum variants induce divergent endothelial transcriptional responses during co culture |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0295053&type=printable |
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