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

Autor: Sampaio NG; Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.; Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia., Emery SJ; Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.; Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia., Garnham AL; Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia.; Bioinformatics Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia., Tan QY; Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.; Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia., Sisquella X; Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia.; Infection and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia., Pimentel MA; Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia.; Infection and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia., Jex AR; Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.; Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia.; Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, Victoria, Australia., Regev-Rudzki N; Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia.; Infection and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia., Schofield L; Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.; Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, Queensland, Australia., Eriksson EM; Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.; Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia.
Jazyk: angličtina
Zdroj: Cellular microbiology [Cell Microbiol] 2018 May; Vol. 20 (5), pp. e12822. Date of Electronic Publication: 2018 Feb 15.
DOI: 10.1111/cmi.12822
Abstrakt: 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.
(© 2018 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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