Extracellular vesicles from early-stage P. falciparum-infected red blood cells contain PfEMP1 and induce transcriptional changes in human monocytes
Details
Publication Year 2018-01-18, Volume 20, Issue #5, Page e12822
Journal Title
Cellular Microbiology
Publication Type
Journal Article
Abstract
Pathogens can release extracellular vesicles (EVs) for cell-cell communication and host modulation. EVs from Plasmodium falciparum, the deadliest malaria parasite species, can transfer drug resistance genes between parasites. EVs from late-stage parasite-infected RBC (iRBC-EVs) are immunostimulatory and affect endothelial cell permeability, but little is known about EVs from early-stage iRBC. We detected the parasite virulence factor PfEMP1, which is responsible for iRBC adherence and a major contributor to disease severity, in EVs only up to 12 hours-post RBC invasion. Furthermore, using PfEMP1 transport knock-out parasites, we determined that EVs originated from inside the iRBC rather than the iRBC surface. Proteomic analysis detected 101 parasite and 178 human proteins in iRBC-EVs. Primary human monocytes stimulated with iRBC-EVs released low levels of inflammatory cytokines, and showed transcriptomic changes. Stimulation with iRBC-EVs from PfEMP1 knock-out parasites induced more gene expression changes, and affected pathways involved in defense response, stress response, and response to cytokines, suggesting a novel function of PfEMP1 when present in EVs. We show for the first time the presence of PfEMP1 in early-stage P. falciparum iRBC-EVs, and the effects of these EVs on primary human monocytes, uncovering a new mechanism of potential parasite pathogenesis and host interaction.
Publisher
Wiley
WEHI Research Division(s)
Population Health And Immunity; Bioinformatics
PubMed ID
29349926
Publisher's Version
https://doi.org/10.1111/cmi.12822
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2018-03-27 09:20:17
Last Modified: 2019-06-20 01:01:26
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