Exploring experimental cerebral malaria pathogenesis through the characterisation of host-derived plasma microparticle protein content

Natalia Tiberti, Sharissa L. Latham, Stephen Bush, Amy Cohen, Robert O. Opoka, Chandy John, Annette Juillard, Georges E. Grau, Valéry Combes

Research output: Contribution to journalArticle

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Abstract

Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection responsible for thousands of deaths in children in sub-Saharan Africa. CM pathogenesis remains incompletely understood but a number of effectors have been proposed, including plasma microparticles (MP). MP numbers are increased in CM patients' circulation and, in the mouse model, they can be localised within inflamed vessels, suggesting their involvement in vascular damage. In the present work we define, for the first time, the protein cargo of MP during experimental cerebral malaria (ECM) with the overarching hypothesis that this characterisation could help understand CM pathogenesis. Using qualitative and quantitative high-throughput proteomics we compared MP proteins from non-infected and P. berghei ANKA-infected mice. More than 360 proteins were identified, 60 of which were differentially abundant, as determined by quantitative comparison using TMT TM isobaric labelling. Network analyses showed that ECM MP carry proteins implicated in molecular mechanisms relevant to CM pathogenesis, including endothelial activation. Among these proteins, the strict association of carbonic anhydrase I and S100A8 with ECM was verified by western blot on MP from DBA/1 and C57BL/6 mice. These results demonstrate that MP protein cargo represents a novel ECM pathogenic trait to consider in the understanding of CM pathogenesis.

Original languageEnglish (US)
Article number37871
JournalScientific Reports
Volume6
DOIs
StatePublished - Dec 5 2016
Externally publishedYes

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Cerebral Malaria
Blood Proteins
Proteins
Carbonic Anhydrase I
Africa South of the Sahara
Plasmodium falciparum
Inbred C57BL Mouse
Proteomics
Malaria
Blood Vessels
Western Blotting

ASJC Scopus subject areas

  • General

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Exploring experimental cerebral malaria pathogenesis through the characterisation of host-derived plasma microparticle protein content. / Tiberti, Natalia; Latham, Sharissa L.; Bush, Stephen; Cohen, Amy; Opoka, Robert O.; John, Chandy; Juillard, Annette; Grau, Georges E.; Combes, Valéry.

In: Scientific Reports, Vol. 6, 37871, 05.12.2016.

Research output: Contribution to journalArticle

Tiberti, Natalia ; Latham, Sharissa L. ; Bush, Stephen ; Cohen, Amy ; Opoka, Robert O. ; John, Chandy ; Juillard, Annette ; Grau, Georges E. ; Combes, Valéry. / Exploring experimental cerebral malaria pathogenesis through the characterisation of host-derived plasma microparticle protein content. In: Scientific Reports. 2016 ; Vol. 6.
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