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

Sampaio, Natália G.; Emery, Samantha J.; Garnham, Alexandra L.; Tan, Qiao Ye; Sisquella, Xavier; Pimentel, Matthew A.; Jex, Aaron R.; Regev‐Rudzki, Neta; Schofield, Louis; Eriksson, Emily M.

doi:10.1111/cmi.12822

Cited by 59 publications

(77 citation statements)

References 72 publications

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“…PHIST proteins such as members of the PFEMP1 trafficking protein (PTP) contribute to cytoadherence by mediating the successful trafficking of PfEMP1 from the Maurer's cleft to the host cell surface 43 . Additionally, PTP2 mediate cell-cell communication by trafficking exosome-like vesicles between infected erythrocytes, a phenomenon which modulates host immune response and increase gametocytogenesis [73][74][75] . The contents of these vesicles range from parasite DNA, RNA and PfEMP1 proteins 74,76 .…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, PTP2 mediate cell-cell communication by trafficking exosome-like vesicles between infected erythrocytes, a phenomenon which modulates host immune response and increase gametocytogenesis [73][74][75] . The contents of these vesicles range from parasite DNA, RNA and PfEMP1 proteins 74,76 . Elevated expression of exported protein genes in SP parasites may thus have physiological relevance, as these proteins could potentially affect the rigidity of the erythrocyte membrane to withstand the stress imposed by moving suspension culture conditions, mediate effective communication among parasites, modulate gametocyte production, etc.…”

Section: Discussionmentioning

confidence: 99%

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Investigating a Plasmodium falciparum erythrocyte invasion phenotype switch at the whole transcriptome level

Nyarko

Tarr

Aniweh

et al. 2020

Sci Rep

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the central role that erythrocyte invasion plays in Plasmodium falciparum survival and reproduction makes this process an attractive target for therapeutic or vaccine development. However, multiple invasion-related genes with complementary and overlapping functions afford the parasite the plasticity to vary ligands used for invasion, leading to phenotypic variation and immune evasion. Overcoming the challenge posed by redundant ligands requires a deeper understanding of conditions that select for variant phenotypes and the molecular mediators. While host factors including receptor heterogeneity and acquired immune responses may drive parasite phenotypic variation, we have previously shown that host-independent changes in invasion phenotype can be achieved by continuous culturing of the W2mef and Dd2 P. falciparum strains in moving suspension as opposed to static conditions. Here, we have used a highly biologically replicated whole transcriptome sequencing approach to identify the molecular signatures of variation associated with the phenotype switch. The data show increased expression of particular invasion-related genes in switched parasites, as well as a large number of genes encoding proteins that are either exported or form part of the export machinery. The genes with most markedly increased expression included members of the erythrocyte binding antigens (EBA), reticulocyte binding homologues (RH), surface associated interspersed proteins (SURFIN), exported protein family 1 (EPF1) and Plasmodium Helical Interspersed Sub-Telomeric (PHIST) gene families. the data indicate changes in expression of a repertoire of genes not previously associated with erythrocyte invasion phenotypes, suggesting the possibility that moving suspension culture may also select for other traits.Plasmodium falciparum malaria remains a major global public health challenge 1-3 . The 48-hour cyclical asexual replication of the blood stage parasite is responsible for the clinical symptoms of the infection 4 . Parasite control is hampered by genetic and phenotypic variations that impact negatively on drug and vaccine development strategies. Thus, a better understanding of the molecular mechanisms responsible for parasite phenotypic variation is important for the development and application of new malaria control strategies.Erythrocyte invasion by P. falciparum merozoites has been a subject of significant research interest due to its central role in parasite survival and transmission 5-7 . Some of these studies have demonstrated the importance of invasion-related gene families in the parasite genome, particularly the erythrocyte binding antigens (EBAs) and reticulocyte binding-like homologues (RHs) 5,8-16 . The array of different genes involved in invasion allows the parasite to vary ligands used for invasion [17][18][19][20] , enabling adaptation to differences in host environments including erythrocyte receptor heterogeneity and ligand-specific immune responses [21][22][23][24][25] . Expression and usage of particular ligands appear to depe...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Investigating a Plasmodium falciparum erythrocyte invasion phenotype switch at the whole transcriptome level

Nyarko

Tarr

Aniweh

et al. 2020

Sci Rep

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“…The EV containing PfEMP1 profoundly modified the proteome of fresh primary human monocytes, and triggered them to release several cytokines and chemokines, including IL‐12p40, CCL2 (MCP‐1), and CCL4 (MIP‐1β). Therefore, these findings point toward an unsuspected role of early stages in CM pathogenesis …”

Section: Examples Of Infectious Diseases With Ev Involvement In Theirmentioning

confidence: 87%

Extracellular vesicles as mediators of immunopathology in infectious diseases

Hosseini‐Beheshti

Grau

2018

Immunol Cell Biol

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In the last decades, extracellular vesicles have emerged as important elements in cell-cell communication and as key players in disease pathogenesis via transmission of their cargo between different cells. Various works have described different subpopulations of these membrane structures, based on their cell of origin, biogenesis, size, biophysical properties and cargo. In addition to their pathophysiological role in the development and progression of different diseases including infectious diseases, neurodegenerative disorders and cancer, extracellular vesicles are now recognized for their potential as novel therapeutic targets and intelligent drug delivery system. Here, we have reviewed the most recent data on different subtypes of extracellular vesicles, focusing on microvesicles and exosomes and their subpopulations, their involvement in immune-mediated pathogenesis of various infectious diseases and their role as potential therapeutic targets.

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“…In fact, EVs might have different composition and therefore different properties depending on the timing of release during the maturation of the parasite. For example, the parasite virulence factor PfEMP1 is detected in EVs only up to 12 h post-RBC invasion (118). When human primary monocytes are treated with EVs from PfEMP1 deficient parasites, they express more genes associated with the defense mechanisms, which suggests a role for EV PfEMP1 in suppressing the immune response (118).…”

Section: Immune Cells and Evsmentioning

confidence: 99%

Role of Extracellular Vesicles in Cellular Cross Talk in Malaria

et al. 2020

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Malaria infection caused by the Plasmodium species is a complex disease in which a fine balance between host and parasite factors determine the disease severity. While in some individuals, the infection will trigger only a mild and uncomplicated disease, other individuals will develop severe complications which lead to death. Extracellular vesicles (EVs) secreted by infected red blood cells (iRBCs), as well as other host cells, are important regulators of the balance that determines the disease outcome. In addition, EVs constitute a robust mode of cell-to-cell communication by transferring signaling cargoes between parasites, and between parasites and host, without requiring cellular contact. The transfer of membrane and cytosolic proteins, lipids, DNA, and RNA through EVs not only modulate the immune response, it also mediates cellular communication between parasites to synchronize the transmission stage. Here, we review the recent progress in understanding EV roles during malaria.

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

Cited by 59 publications

References 72 publications

Investigating a Plasmodium falciparum erythrocyte invasion phenotype switch at the whole transcriptome level

Investigating a Plasmodium falciparum erythrocyte invasion phenotype switch at the whole transcriptome level

Extracellular vesicles as mediators of immunopathology in infectious diseases

Role of Extracellular Vesicles in Cellular Cross Talk in Malaria

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