<named-content content-type="genus-species">Plasmodium falciparum</named-content> Histidine-Rich Protein II Compromises Brain Endothelial Barriers and May Promote Cerebral Malaria Pathogenesis

ABSTRACT Cerebral malaria (CM) is a disease of the vascular endothelium caused by Plasmodium falciparum. It is characterized by parasite sequestration, inflammatory cytokine production, and vascular leakage. A distinguishing feature of P. falciparum infection is parasite production and secretion of...

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Autores principales:	Priya Pal, Brian P. Daniels, Anna Oskman, Michael S. Diamond, Robyn S. Klein, Daniel E. Goldberg
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2016
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/267b0871b94546c6bd373e0d944c0941
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spelling	oai:doaj.org-article:267b0871b94546c6bd373e0d944c09412021-11-15T15:50:16Z<named-content content-type="genus-species">Plasmodium falciparum</named-content> Histidine-Rich Protein II Compromises Brain Endothelial Barriers and May Promote Cerebral Malaria Pathogenesis10.1128/mBio.00617-162150-7511https://doaj.org/article/267b0871b94546c6bd373e0d944c09412016-07-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00617-16https://doaj.org/toc/2150-7511ABSTRACT Cerebral malaria (CM) is a disease of the vascular endothelium caused by Plasmodium falciparum. It is characterized by parasite sequestration, inflammatory cytokine production, and vascular leakage. A distinguishing feature of P. falciparum infection is parasite production and secretion of histidine-rich protein II (HRPII). Plasma HRPII is a diagnostic and prognostic marker for falciparum malaria. We demonstrate that disruption of a human cerebral microvascular endothelial barrier by P. falciparum-infected erythrocytes depends on expression of HRPII. Purified recombinant or native HRPII can recapitulate these effects. HRPII action occurs via activation of the inflammasome, resulting in decreased integrity of tight junctions and increased endothelial permeability. We propose that HRPII is a virulence factor that may contribute to cerebral malaria by compromising endothelial barrier integrity within the central nervous system. IMPORTANCE Cerebral malaria is a devastating disease. Patients have high levels of the protein HRPII in their blood. We have found that endothelial cell barriers become leaky when treated with concentrations of HRPII similar to those found in patients. This result suggests that HRPII may be important in cerebral malaria. Our finding that HRPII functions by causing inflammation suggests points of intervention for therapy or vaccination against this disease.Priya PalBrian P. DanielsAnna OskmanMichael S. DiamondRobyn S. KleinDaniel E. GoldbergAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 7, Iss 3 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Priya Pal Brian P. Daniels Anna Oskman Michael S. Diamond Robyn S. Klein Daniel E. Goldberg <named-content content-type="genus-species">Plasmodium falciparum</named-content> Histidine-Rich Protein II Compromises Brain Endothelial Barriers and May Promote Cerebral Malaria Pathogenesis
description	ABSTRACT Cerebral malaria (CM) is a disease of the vascular endothelium caused by Plasmodium falciparum. It is characterized by parasite sequestration, inflammatory cytokine production, and vascular leakage. A distinguishing feature of P. falciparum infection is parasite production and secretion of histidine-rich protein II (HRPII). Plasma HRPII is a diagnostic and prognostic marker for falciparum malaria. We demonstrate that disruption of a human cerebral microvascular endothelial barrier by P. falciparum-infected erythrocytes depends on expression of HRPII. Purified recombinant or native HRPII can recapitulate these effects. HRPII action occurs via activation of the inflammasome, resulting in decreased integrity of tight junctions and increased endothelial permeability. We propose that HRPII is a virulence factor that may contribute to cerebral malaria by compromising endothelial barrier integrity within the central nervous system. IMPORTANCE Cerebral malaria is a devastating disease. Patients have high levels of the protein HRPII in their blood. We have found that endothelial cell barriers become leaky when treated with concentrations of HRPII similar to those found in patients. This result suggests that HRPII may be important in cerebral malaria. Our finding that HRPII functions by causing inflammation suggests points of intervention for therapy or vaccination against this disease.
format	article
author	Priya Pal Brian P. Daniels Anna Oskman Michael S. Diamond Robyn S. Klein Daniel E. Goldberg
author_facet	Priya Pal Brian P. Daniels Anna Oskman Michael S. Diamond Robyn S. Klein Daniel E. Goldberg
author_sort	Priya Pal
title	<named-content content-type="genus-species">Plasmodium falciparum</named-content> Histidine-Rich Protein II Compromises Brain Endothelial Barriers and May Promote Cerebral Malaria Pathogenesis
title_short	<named-content content-type="genus-species">Plasmodium falciparum</named-content> Histidine-Rich Protein II Compromises Brain Endothelial Barriers and May Promote Cerebral Malaria Pathogenesis
title_full	<named-content content-type="genus-species">Plasmodium falciparum</named-content> Histidine-Rich Protein II Compromises Brain Endothelial Barriers and May Promote Cerebral Malaria Pathogenesis
title_fullStr	<named-content content-type="genus-species">Plasmodium falciparum</named-content> Histidine-Rich Protein II Compromises Brain Endothelial Barriers and May Promote Cerebral Malaria Pathogenesis
title_full_unstemmed	<named-content content-type="genus-species">Plasmodium falciparum</named-content> Histidine-Rich Protein II Compromises Brain Endothelial Barriers and May Promote Cerebral Malaria Pathogenesis
title_sort	<named-content content-type="genus-species">plasmodium falciparum</named-content> histidine-rich protein ii compromises brain endothelial barriers and may promote cerebral malaria pathogenesis
publisher	American Society for Microbiology
publishDate	2016
url	https://doaj.org/article/267b0871b94546c6bd373e0d944c0941
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<named-content content-type="genus-species">Plasmodium falciparum</named-content> Histidine-Rich Protein II Compromises Brain Endothelial Barriers and May Promote Cerebral Malaria Pathogenesis

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