Extracellular vesicles from early-stage P. falciparum-infected red blood cells contain PfEMP1 and induce transcriptional changes in human monocytes

Sampaio, NG; Emery, S; Garnham, A; Tan, QY; Sisquella, X; Pimentel, MA; Regev-Rudzki, N; Schofield, L; Eriksson, EM

Author(s): Sampaio, NG; Emery, S; Garnham, A; Tan, QY; Sisquella, X; Pimentel, MA; Regev-Rudzki, N; Schofield, L; Eriksson, EM;
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
Research Division(s): Population Health And Immunity; Bioinformatics
PubMed ID: 29349926
Publisher's Version: https://doi.org/10.1111/cmi.12822
Terms of Use/Rights Notice: Refer to copyright notice on published article.
Documents: Sampaio NG et al_Cell Microbiology 2018 author manuscript.pdf - (1.97MB, application/pdf)

Creation Date: 2018-03-27 09:20:17

Last Modified: 2019-06-20 01:01:26