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

Authors

Natalia Tiberti, University of Technology Sydney, Australia.
Sharissa L. Latham, The University of Sydney, Australia.
Stephen Bush, University of Technology Sydney, Australia.
Amy Cohen, The University of Sydney, Australia.
Robert Opoka, Aga Khan UniversityFollow
Chandy C. John, Indiana University School of Medicine, United States of America.
Annette Juillard, The University of Sydney, Australia.
Georges E. Grau, The University of Sydney, Australia.
Valéry Combes, University of Technology Sydney, Australia.

Document Type

Report

Department

Paediatrics and Child Health (East Africa)

Abstract

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.

Comments

This work was published before the author joined Aga Khan University.

Publication (Name of Journal)

Scientific Report

DOI

10.1038/srep37871

Recommended Citation

Tiberti, N., Latham, S. L., Bush, S., Cohen, A., Opoka, R., John, C. C., Juillard, A., Grau, G. E., Combes, V. (2016). Exploring experimental cerebral malaria pathogenesis through the characterisation of host-derived plasma microparticle protein content. Scientific Report, 1-15.
Available at: https://ecommons.aku.edu/eastafrica_fhs_mc_paediatr_child_health/438