Plasmodium falciparum histidine-rich protein II causes vascular leakage and exacerbates experimental cerebral malaria in mice

Priya Pal, Amanda E. Balaban, Michael S. DIamond, Photini Sinnis, Robyn S. Klein, Daniel E. Goldberg

Research output: Contribution to journalArticle

Abstract

A devastating complication of Plasmodium falciparum infection is cerebral malaria, in which vascular leakage and cerebral swelling lead to coma and often death. P. falciparum produces a protein called histidine-rich protein II (HRPII) that accumulates to high levels in the bloodstream of patients and serves as a diagnostic and prognostic marker for falciparum malaria. Using a human cerebral microvascular endothelial barrier model, we previously found that HRPII activates the endothelial cell inflammasome, resulting in decreased integrity of tight junctions and increased endothelial barrier permeability. Here, we report that intravenous administration of HRPII induced blood-brain barrier leakage in uninfected mice. Furthermore, HRPII infusion in P. berghei-infected mice increased early mortality from experimental cerebral malaria. These data support the hypothesis that HRPII is a virulence factor that contributes to cerebral malaria by compromising the integrity of the blood-brain barrier.

Original languageEnglish (US)
Article numbere0177142
JournalPLoS One
Volume12
Issue number5
DOIs
StatePublished - May 1 2017

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Cerebral Malaria
Plasmodium falciparum
histidine
blood vessels
Blood Vessels
mice
Blood-Brain Barrier
blood-brain barrier
proteins
Inflammasomes
Falciparum Malaria
Tight Junctions
Endothelial cells
Virulence Factors
coma
Coma
tight junctions
Intravenous Administration
Malaria
Swelling

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Plasmodium falciparum histidine-rich protein II causes vascular leakage and exacerbates experimental cerebral malaria in mice. / Pal, Priya; Balaban, Amanda E.; DIamond, Michael S.; Sinnis, Photini; Klein, Robyn S.; Goldberg, Daniel E.

In: PLoS One, Vol. 12, No. 5, e0177142, 01.05.2017.

Research output: Contribution to journalArticle

Pal, Priya ; Balaban, Amanda E. ; DIamond, Michael S. ; Sinnis, Photini ; Klein, Robyn S. ; Goldberg, Daniel E. / Plasmodium falciparum histidine-rich protein II causes vascular leakage and exacerbates experimental cerebral malaria in mice. In: PLoS One. 2017 ; Vol. 12, No. 5.
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