Interaction between Endothelial Protein C Receptor and Intercellular Adhesion Molecule 1 to Mediate Binding of <named-content content-type="genus-species">Plasmodium falciparum</named-content>-Infected Erythrocytes to Endothelial Cells

ABSTRACT Intercellular adhesion molecule 1 (ICAM-1) and the endothelial protein C receptor (EPCR) are candidate receptors for the deadly complication cerebral malaria. However, it remains unclear if Plasmodium falciparum parasites with dual binding specificity are involved in cytoadhesion or differe...

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Autores principales:	Marion Avril, Maria Bernabeu, Maxwell Benjamin, Andrew Jay Brazier, Joseph D. Smith
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2016
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/680f8fcb41bb44bf9f54ad50503af282
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spelling	oai:doaj.org-article:680f8fcb41bb44bf9f54ad50503af2822021-11-15T15:50:18ZInteraction between Endothelial Protein C Receptor and Intercellular Adhesion Molecule 1 to Mediate Binding of <named-content content-type="genus-species">Plasmodium falciparum</named-content>-Infected Erythrocytes to Endothelial Cells10.1128/mBio.00615-162150-7511https://doaj.org/article/680f8fcb41bb44bf9f54ad50503af2822016-09-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00615-16https://doaj.org/toc/2150-7511ABSTRACT Intercellular adhesion molecule 1 (ICAM-1) and the endothelial protein C receptor (EPCR) are candidate receptors for the deadly complication cerebral malaria. However, it remains unclear if Plasmodium falciparum parasites with dual binding specificity are involved in cytoadhesion or different parasite subpopulations bind in brain microvessels. Here, we investigated this issue by studying different subtypes of ICAM-1-binding parasite lines. We show that two parasite lines expressing domain cassette 13 (DC13) of the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family have dual binding specificity for EPCR and ICAM-1 and further mapped ICAM-1 binding to the first DBLβ domain following the PfEMP1 head structure in both proteins. As PfEMP1 head structures have diverged between group A (EPCR binders) and groups B and C (CD36 binders), we also investigated how ICAM-1-binding parasites with different coreceptor binding traits influence P. falciparum-infected erythrocyte binding to endothelial cells. Whereas levels of binding to tumor necrosis factor alpha (TNF-α)-stimulated endothelial cells from the lung and brain by all ICAM-1-binding parasite lines increased, group A (EPCR and ICAM-1) was less dependent than group B (CD36 and ICAM-1) on ICAM-1 upregulation. Furthermore, both group A DC13 parasite lines had higher binding levels to brain endothelial cells (a microvascular niche with limited CD36 expression). This study shows that ICAM-1 is a coreceptor for a subset of EPCR-binding parasites and provides the first evidence of how EPCR and ICAM-1 interact to mediate parasite binding to both resting and TNF-α-activated primary brain and lung endothelial cells. IMPORTANCE Cerebral malaria is a severe neurological complication of P. falciparum infection associated with infected erythrocyte (IE) binding in cerebral vessels. Yet little is known about the mechanisms by which parasites adhere in the brain or other microvascular sites. Here, we studied parasite lines expressing group A DC13-containing PfEMP1 variants, a subset that has previously been shown to have high brain cell- and other endothelial cell-binding activities. We show that DC13-containing PfEMP1 variants have dual EPCR- and ICAM-1-binding activities and that both receptors are involved in parasite adherence to lung and brain endothelial cells. As both EPCR and ICAM-1 are implicated in cerebral malaria, these findings suggest the possibility that parasites with dual binding activities are involved in parasite sequestration to microvascular beds with low CD36 expression, such as the brain, and we urge more research into the multiadhesive properties of PfEMP1 variants.Marion AvrilMaria BernabeuMaxwell BenjaminAndrew Jay BrazierJoseph D. SmithAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 7, Iss 4 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Marion Avril Maria Bernabeu Maxwell Benjamin Andrew Jay Brazier Joseph D. Smith Interaction between Endothelial Protein C Receptor and Intercellular Adhesion Molecule 1 to Mediate Binding of <named-content content-type="genus-species">Plasmodium falciparum</named-content>-Infected Erythrocytes to Endothelial Cells
description	ABSTRACT Intercellular adhesion molecule 1 (ICAM-1) and the endothelial protein C receptor (EPCR) are candidate receptors for the deadly complication cerebral malaria. However, it remains unclear if Plasmodium falciparum parasites with dual binding specificity are involved in cytoadhesion or different parasite subpopulations bind in brain microvessels. Here, we investigated this issue by studying different subtypes of ICAM-1-binding parasite lines. We show that two parasite lines expressing domain cassette 13 (DC13) of the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family have dual binding specificity for EPCR and ICAM-1 and further mapped ICAM-1 binding to the first DBLβ domain following the PfEMP1 head structure in both proteins. As PfEMP1 head structures have diverged between group A (EPCR binders) and groups B and C (CD36 binders), we also investigated how ICAM-1-binding parasites with different coreceptor binding traits influence P. falciparum-infected erythrocyte binding to endothelial cells. Whereas levels of binding to tumor necrosis factor alpha (TNF-α)-stimulated endothelial cells from the lung and brain by all ICAM-1-binding parasite lines increased, group A (EPCR and ICAM-1) was less dependent than group B (CD36 and ICAM-1) on ICAM-1 upregulation. Furthermore, both group A DC13 parasite lines had higher binding levels to brain endothelial cells (a microvascular niche with limited CD36 expression). This study shows that ICAM-1 is a coreceptor for a subset of EPCR-binding parasites and provides the first evidence of how EPCR and ICAM-1 interact to mediate parasite binding to both resting and TNF-α-activated primary brain and lung endothelial cells. IMPORTANCE Cerebral malaria is a severe neurological complication of P. falciparum infection associated with infected erythrocyte (IE) binding in cerebral vessels. Yet little is known about the mechanisms by which parasites adhere in the brain or other microvascular sites. Here, we studied parasite lines expressing group A DC13-containing PfEMP1 variants, a subset that has previously been shown to have high brain cell- and other endothelial cell-binding activities. We show that DC13-containing PfEMP1 variants have dual EPCR- and ICAM-1-binding activities and that both receptors are involved in parasite adherence to lung and brain endothelial cells. As both EPCR and ICAM-1 are implicated in cerebral malaria, these findings suggest the possibility that parasites with dual binding activities are involved in parasite sequestration to microvascular beds with low CD36 expression, such as the brain, and we urge more research into the multiadhesive properties of PfEMP1 variants.
format	article
author	Marion Avril Maria Bernabeu Maxwell Benjamin Andrew Jay Brazier Joseph D. Smith
author_facet	Marion Avril Maria Bernabeu Maxwell Benjamin Andrew Jay Brazier Joseph D. Smith
author_sort	Marion Avril
title	Interaction between Endothelial Protein C Receptor and Intercellular Adhesion Molecule 1 to Mediate Binding of <named-content content-type="genus-species">Plasmodium falciparum</named-content>-Infected Erythrocytes to Endothelial Cells
title_short	Interaction between Endothelial Protein C Receptor and Intercellular Adhesion Molecule 1 to Mediate Binding of <named-content content-type="genus-species">Plasmodium falciparum</named-content>-Infected Erythrocytes to Endothelial Cells
title_full	Interaction between Endothelial Protein C Receptor and Intercellular Adhesion Molecule 1 to Mediate Binding of <named-content content-type="genus-species">Plasmodium falciparum</named-content>-Infected Erythrocytes to Endothelial Cells
title_fullStr	Interaction between Endothelial Protein C Receptor and Intercellular Adhesion Molecule 1 to Mediate Binding of <named-content content-type="genus-species">Plasmodium falciparum</named-content>-Infected Erythrocytes to Endothelial Cells
title_full_unstemmed	Interaction between Endothelial Protein C Receptor and Intercellular Adhesion Molecule 1 to Mediate Binding of <named-content content-type="genus-species">Plasmodium falciparum</named-content>-Infected Erythrocytes to Endothelial Cells
title_sort	interaction between endothelial protein c receptor and intercellular adhesion molecule 1 to mediate binding of <named-content content-type="genus-species">plasmodium falciparum</named-content>-infected erythrocytes to endothelial cells
publisher	American Society for Microbiology
publishDate	2016
url	https://doaj.org/article/680f8fcb41bb44bf9f54ad50503af282
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Interaction between Endothelial Protein C Receptor and Intercellular Adhesion Molecule 1 to Mediate Binding of <named-content content-type="genus-species">Plasmodium falciparum</named-content>-Infected Erythrocytes to Endothelial Cells

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