Proteomic identification of the contents of small extracellular vesicles from in vivo Plasmodium yoelii infection

De Sousa, Karina P., Potriquet, Jeremy, Mulvenna, Jason, Sotillo-Gallego, Javier, Groves, Penny L., Loukas, Alex, Apte, Simon H., and Doolan, Denise L. (2022) Proteomic identification of the contents of small extracellular vesicles from in vivo Plasmodium yoelii infection. International Journal for Parasitology, 52 (1). pp. 35-45.

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Abstract

Small extracellular vesicles, including exosomes, are formed by the endocytic pathway and contain genetic and protein material which reflect the contents of their cells of origin. These contents have a role in vesicle-mediated information transfer, as well as physiological and pathological functions. Thus, these vesicles are of great interest as therapeutic targets, or as vehicles for immunomodulatory control. In Plasmodium spp. infections, vesicles derived from the parasite or parasite-infected cells have been shown to induce the expression of pro-inflammatory elements, which have been correlated with manifestations of clinical disease. Herein, we characterised the protein cargo of naturally occurring sEVs in the plasma of P. yoelii-infected mice. After in vivo infections, extracellular vesicles in the size range of exosomes were collected by sequential centrifugation/ultracentrifugation followed by isopycnic gradient separation. Analysis of the vesicles was performed by transmission electron microscopy, dynamic light scattering, SDS–PAGE and flow cytometry. LC-MS analysis followed by bioinformatics analysis predicted parasite protein cargo associated with exosomes. Within these small extracellular vesicles, we identified proteins of interest as vaccine candidates, uncharacterized proteins which may be targets of T cell immunoreactivity, and proteins involved in metabolic processes, regulation, homeostasis and immunity. Importantly, the small extracellular vesicles studied in our work were obtained from in vivo infection rather than from the supernatant of in vitro cultures. These findings add to the growing interest in parasite small extracellular vesicles, further our understanding of the interactions between host and parasite, and identify novel proteins which may represent potential targets for vaccination against malaria.

Item ID: 72692
Item Type: Article (Research - C1)
ISSN: 1879-0135
Keywords: Extracellular vesicles, Exosomes, Plasmodium, Malaria, Immunomodulation, Proteomics
Copyright Information: © 2021 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.
Funders: National Health and Medical Research Council (NHMRC)
Projects and Grants: NHMRC 1037304, NHMRC 1023636
Date Deposited: 06 Jun 2022 06:43
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3207 Medical microbiology > 320704 Medical parasitology @ 100%
SEO Codes: 20 HEALTH > 2001 Clinical health > 200104 Prevention of human diseases and conditions @ 100%
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