Plasma mEV levels in Ghanain malaria patients with low parasitaemia are higher than those of healthy controls, raising the potential for parasite markers in mEVs as diagnostic targets

Antwi‐Baffour, Samuel; Malibha-Pinchbeck, Memory; Stratton, Dan; Jorfi, Samireh; Lange, Sigrun; Inal, Jameel M.

doi:10.1080/20013078.2019.1697124

Cited by 27 publications

(30 citation statements)

References 84 publications

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“…Indeed, in teleost, it has been reported that changes in EV numbers and EV deimination protein and microRNA cargo can be a biomarker for environmental temperature factors [ 33 ] and, in response to other stressors, teleost plasma EVs have been found enriched with Hsp70 [ 46 ] and selected micro-RNAs [ 47 ]. In human parasitic disease, EV profiles can also be indicative of infection status [ 48 ]. Therefore, the characterisation of EVs across a wide range of taxa further highlights their potential for biomarker application or “EV-fingerprinting” for the assessment of animal health.…”

Section: Discussionmentioning

confidence: 99%

The Proteome and Citrullinome of Hippoglossus hippoglossus Extracellular Vesicles—Novel Insights into Roles of the Serum Secretome in Immune, Gene Regulatory and Metabolic Pathways

Magnadóttir

Kraev

Dodds

et al. 2021

IJMS

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Extracellular vesicles (EVs) are lipid bilayer vesicles which are released from cells and play multifaceted roles in cellular communication in health and disease. EVs can be isolated from various body fluids, including serum and plasma, and are usable biomarkers as they can inform health status. Studies on EVs are an emerging research field in teleost fish, with accumulating evidence for important functions in immunity and homeostasis, but remain to be characterised in most fish species, including halibut. Protein deimination is a post-translational modification caused by a conserved family of enzymes, named peptidylarginine deiminases (PADs), and results in changes in protein folding and function via conversion of arginine to citrulline in target proteins. Protein deimination has been recently described in halibut ontogeny and halibut serum. Neither EV profiles, nor total protein or deiminated protein EV cargos have yet been assessed in halibut and are reported in the current study. Halibut serum EVs showed a poly-dispersed population in the size range of 50–600 nm, with modal size of EVs falling at 138 nm, and morphology was further confirmed by transmission electron microscopy. The assessment of EV total protein cargo revealed 124 protein hits and 37 deiminated protein hits, whereof 15 hits were particularly identified in deiminated form only. Protein interaction network analysis showed that deimination hits are involved in a range of gene regulatory, immune, metabolic and developmental processes. The same was found for total EV protein cargo, although a far wider range of pathways was found than for deimination hits only. The expression of complement component C3 and C4, as well as pentraxin-like protein, which were identified by proteomic analysis, was further verified in EVs by western blotting. This showed that C3 is exported in EVs at higher levels than C4 and deiminated C3 was furthermore confirmed to be at high levels in the deimination-enriched EV fractions, while, in comparison, C4 showed very low detection in deimination-enriched EV fractions. Pentraxin was exported in EVs, but not detected in the deimination-enriched fractions. Our findings provide novel insights into EV-mediated communication in halibut serum, via transport of protein cargo, including post-translationally deiminated proteins.

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Section: Discussionmentioning

confidence: 99%

The Proteome and Citrullinome of Hippoglossus hippoglossus Extracellular Vesicles—Novel Insights into Roles of the Serum Secretome in Immune, Gene Regulatory and Metabolic Pathways

Magnadóttir

Kraev

Dodds

et al. 2021

IJMS

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“… 16 , 17 ). We and others have previously shown that malaria parasites release EVs during their blood-stage to deliver cargo between them and to their host 18 – 23 . Specifically, the parasites deliver cargo to immune and endothelial host cells to promote their growth 6 , 19 , 20 .…”

Section: Introductionmentioning

confidence: 99%

20S proteasomes secreted by the malaria parasite promote its growth

et al. 2021

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Mature red blood cells (RBCs) lack internal organelles and canonical defense mechanisms, making them both a fascinating host cell, in general, and an intriguing choice for the deadly malaria parasite Plasmodium falciparum (Pf), in particular. Pf, while growing inside its natural host, the human RBC, secretes multipurpose extracellular vesicles (EVs), yet their influence on this essential host cell remains unknown. Here we demonstrate that Pf parasites, cultured in fresh human donor blood, secrete within such EVs assembled and functional 20S proteasome complexes (EV-20S). The EV-20S proteasomes modulate the mechanical properties of naïve human RBCs by remodeling their cytoskeletal network. Furthermore, we identify four degradation targets of the secreted 20S proteasome, the phosphorylated cytoskeletal proteins β-adducin, ankyrin-1, dematin and Epb4.1. Overall, our findings reveal a previously unknown 20S proteasome secretion mechanism employed by the human malaria parasite, which primes RBCs for parasite invasion by altering membrane stiffness, to facilitate malaria parasite growth.

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“…It is now clear that EVs and their cargo have potential as biomarkers. Their elevated numbers, notably endothelial-, platelet-and RBC-derived MVs, in the circulation of human patients with CM has already been proven in multiple studies [39,84,91] . The role of EVs as a biomarker in severe malaria is still in its infancy and in-depth multi-centre studies are still needed to ascertain their predictive value to improve rapid detection in bodily fluids.…”

Section: Extracellular Vesicle Cargo: Effector Biomarker or Both?mentioning

confidence: 97%

Extracellular vesicles, from pathogenesis to biomarkers: the case for cerebral malaria

Cheng¹,

Sealy²,

Tiberti³

et al. 2020

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Malaria infections due to the Plasmodium parasite remains a major global health problem. Plasmodium falciparum is responsible for majority of the severe cases, resulting in more than 400,000 deaths per annum. Extracellular vesicles (EVs) released by vascular cells, including parasitised erythrocytes, have been detected with increased levels in patients with malaria. EVs are thought to be involved in the pathogenesis of severe malaria, particularly cerebral malaria, and represent a unique molecular signature for different forms of the infection. In this review, we will cover the known effects of EVs on the vasculature and discuss their potential use as a biomarker of disease severity.

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Plasma mEV levels in Ghanain malaria patients with low parasitaemia are higher than those of healthy controls, raising the potential for parasite markers in mEVs as diagnostic targets

Abstract: Inal (2020) Plasma mEV levels in Ghanain malaria patients with low parasitaemia are higher than those of healthy controls, raising the potential for parasite markers in mEVs as diagnostic targets,

Cited by 27 publications

References 84 publications

The Proteome and Citrullinome of Hippoglossus hippoglossus Extracellular Vesicles—Novel Insights into Roles of the Serum Secretome in Immune, Gene Regulatory and Metabolic Pathways

The Proteome and Citrullinome of Hippoglossus hippoglossus Extracellular Vesicles—Novel Insights into Roles of the Serum Secretome in Immune, Gene Regulatory and Metabolic Pathways

20S proteasomes secreted by the malaria parasite promote its growth

Extracellular vesicles, from pathogenesis to biomarkers: the case for cerebral malaria

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