Infected erythrocyte-derived extracellular vesicles alter vascular function via regulatory Ago2-miRNA complexes in malaria.

Mantel, P.-Y. et al. (2016) Infected erythrocyte-derived extracellular vesicles alter vascular function via regulatory Ago2-miRNA complexes in malaria. Nature Communications, 7, 12727. (doi: 10.1038/ncomms12727) (PMID:27721445) (PMCID:PMC5062468)

Abstract

Malaria remains one of the greatest public health challenges worldwide, particularly in sub-Saharan Africa. The clinical outcome of individuals infected with Plasmodium falciparum parasites depends on many factors including host systemic inflammatory responses, parasite sequestration in tissues and vascular dysfunction. Production of pro-inflammatory cytokines and chemokines promotes endothelial activation as well as recruitment and infiltration of inflammatory cells, which in turn triggers further endothelial cell activation and parasite sequestration. Inflammatory responses are triggered in part by bioactive parasite products such as hemozoin and infected red blood cell-derived extracellular vesicles (iRBC-derived EVs). Here we demonstrate that such EVs contain functional miRNA-Argonaute 2 complexes that are derived from the host RBC. Moreover, we show that EVs are efficiently internalized by endothelial cells, where the miRNA-Argonaute 2 complexes modulate target gene expression and barrier properties. Altogether, these findings provide a mechanistic link between EVs and vascular dysfunction during malaria infection.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Marti, Professor Matthias and Brancucci, Dr Nicolas
• Authors: Mantel, P.-Y., Hjelmqvist, D., Walch, M., Kharoubi-Hess, S., Nilsson, S., Ravel, D., Ribeiro, M., Grüring, C., Ma, S., Padmanabhan, P., Trachtenberg, A., Ankarklev, J., Brancucci, N. M., Huttenhower, C., Duraisingh, M. T., Ghiran, I., Kuo, W. P., Filgueira, L., Martinelli, R., and Marti, M.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Nature Communications
• Publisher: Nature Publishing Group
• ISSN: 2041-1723
• ISSN (Online): 2041-1723
• Copyright Holders: Copyright © 2016 The Authors
• First Published: First published in Nature Communications 7:12727
• Publisher Policy: Reproduced under a Creative Commons License