Extracellular vesicles from early stage Plasmodium falciparum‐infected red blood cells contain PfEMP1 and induce transcriptional changes in human monocytes

Sampaio, Natália G., Emery, Samantha J., Garnham, Alexandra L., Tan, Qiao Y., Sisquella, Xavier, Pimentel, Matthew A., Jex, Aaron R., Regev-Rudzki, Neta, Schofield, Louis, and Eriksson, Emily M. (2018) Extracellular vesicles from early stage Plasmodium falciparum‐infected red blood cells contain PfEMP1 and induce transcriptional changes in human monocytes. Cellular Microbiology, 20 (5). e12822.

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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‐hr post‐RBC invasion. Furthermore, using PfEMP1 transport knockout 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 knockout parasites induced more gene expression changes and affected pathways involved in defence 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.

Item ID: 53576
Item Type: Article (Research - C1)
ISSN: 1462-5822
Keywords: diseases, extracellular vesicles, immunology, infection, proteomics, transcriptomics
Copyright Information: © 2018 John Wiley & Sons Ltd
Funders: National Health and Medical Research Council (NHMRC)
Projects and Grants: NHMRC grant APP106722, NHMRC grant APP1126395, NHMRC Dora Lush Scholarship APP1038030
Date Deposited: 09 May 2018 08:24
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1108 Medical Microbiology > 110803 Medical Parasitology @ 50%
11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110707 Innate Immunity @ 50%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 50%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 50%
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