Malaria Parasites Distribute Subversive Messages across Enemy Lines

Rivkin, Anna; Ben-Hur, Sharon; Regev‐Rudzki, Neta

doi:10.1016/j.pt.2016.11.005

Cited by 5 publications

(5 citation statements)

References 10 publications

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“…A case in point, VCAM1 is indirectly regulated by TNF 30 , a predicted target of miR–19b–3p. These results support a study indicating that iRBC-derived vesicles carry functional human regulatory miRNAs to host endothelial cells and regulate VCAM1 expression in a yet unknown mechanism 23 , 31 .…”

Section: Resultssupporting

confidence: 90%

“…In addition, the predicted targets of the human miRNAs within the vesicles are genes involved in cell adhesion regulation, including VCAM1, CD36 and ICAM1 receptors, to which different forms of the virulence protein family PfEMP1 bind 64 , 65 . These results strongly support the work published showing that P. falciparum- derived vesicles not only target endothelial cells and deliver functional miR-451a-Argonaute2 complexes (RISC) but that the RNA delivery results in elevation of a number of transcripts of the VCAM1 receptor 23 , 31 . Importunately, traffic of genetic material may serve as a sensing signal in a population to coordinate parasite social interactions 16 , thus potentially playing a role in parasite differentiation into sexual forms as previously observed 19 , 20 .…”

Section: Discussionsupporting

confidence: 90%

“…P. falciparum -infected RBC (iRBC)-derived EVs have a function in parasite–parasite communication and promote the differentiation of parasites in recipient cells to gametocytes 19 , 20 . Malaria parasites also use EVs as a mechanism of intercellular communication to alter host cell responses 21 , 22 using human RNA molecules 21 , 23 .…”

Section: Introductionmentioning

confidence: 99%

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Malaria parasite DNA-harbouring vesicles activate cytosolic immune sensors

et al. 2017

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STING is an innate immune cytosolic adaptor for DNA sensors that engage malaria parasite (Plasmodium falciparum) or other pathogen DNA. As P. falciparum infects red blood cells and not leukocytes, how parasite DNA reaches such host cytosolic DNA sensors in immune cells is unclear. Here we show that malaria parasites inside red blood cells can engage host cytosolic innate immune cell receptors from a distance by secreting extracellular vesicles (EV) containing parasitic small RNA and genomic DNA. Upon internalization of DNA-harboring EVs by human monocytes, P. falciparum DNA is released within the host cell cytosol, leading to STING-dependent DNA sensing. STING subsequently activates the kinase TBK1, which phosphorylates the transcription factor IRF3, causing IRF3 to translocate to the nucleus and induce STING-dependent gene expression. This DNA-sensing pathway may be an important decoy mechanism to promote P. falciparum virulence and thereby may affect future strategies to treat malaria.

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Section: Resultssupporting

confidence: 90%

Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

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Malaria parasite DNA-harbouring vesicles activate cytosolic immune sensors

et al. 2017

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“…Single cell analyses will become important to address questions regarding the dynamics of antigenic variation in vivo , to clarify to what degree parasites maintain clonality with regard to SICAvar/ SICA expression after short-term passage in naïve hosts, and how this clonality may change as a chronic infection is established. Answering such questions is key to understanding variant antigen regulation on a population level and addressing possible implications for cell–cell communication mechanisms relating to switching of variant antigen phenotypes among iRBC (reviewed in Rivkin et al 2017 ) and possible intracellular signalling pathways as suggested in response to host antibodies (Al-Khedery et al 1999 ). Moreover, the combination of population and single-cell transcriptomic studies along with mathematical modelling can quite readily advance understanding of mechanisms of transcriptional and post-transcriptional control, including the possible role(s) of non-coding RNAs, as on/off or antigenic switch changes are occurring over time in SICA[+] and SICA[−] infections, in intact or splenectomized animals.…”

Section: The Quest For Identifying Regulatory Mechanisms Of Antigenicmentioning

confidence: 99%

Plasmodium knowlesi:a superbin vivononhuman primate model of antigenic variation in malaria

et al. 2017

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SUMMARYAntigenic variation in malaria was discovered in Plasmodium knowlesi studies involving longitudinal infections of rhesus macaques (M. mulatta). The variant proteins, known as the P. knowlesi Schizont Infected Cell Agglutination (SICA) antigens and the P. falciparum Erythrocyte Membrane Protein 1 (PfEMP1) antigens, expressed by the SICAvar and var multigene families, respectively, have been studied for over 30 years. Expression of the SICA antigens in P. knowlesi requires a splenic component, and specific antibodies are necessary for variant antigen switch events in vivo. Outstanding questions revolve around the role of the spleen and the mechanisms by which the expression of these variant antigen families are regulated. Importantly, the longitudinal dynamics and molecular mechanisms that govern variant antigen expression can be studied with P. knowlesi infection of its mammalian and vector hosts. Synchronous infections can be initiated with established clones and studied at multi-omic levels, with the benefit of computational tools from systems biology that permit the integration of datasets and the design of explanatory, predictive mathematical models. Here we provide an historical account of this topic, while highlighting the potential for maximizing the use of P. knowlesi – macaque model systems and summarizing exciting new progress in this area of research.

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“…Mantel et al ( 2016 ) reported that tsRNAs of T. cruzi epimastigote MVs have a longer nucleotide sequence than tsRNAs in the T. cruzi subcellular region. Conversely, secreted exosomes of T. brucei containing spliced leader RNA (SL RNA) affected the social motility of procyclic trypanosome with sheer dependence on perceptible genetic signal (Eliaz et al, 2017 ), and P. falciparum -derived vesicles altered cellular function via changes in EV-derived miR-451a-Argonaute2 complexes and target gene expressions (Mantel et al, 2016 ; Rivkin et al, 2017 ). Nevertheless, the potential functions of abundantly detected non-coding RNAs in the P. falciparum- EVs are yet to be clarified (Sisquella et al, 2017 ) as well as the extra nucleotide extension of tsRNAs of T. cruzi MVs.…”

Section: Ppevs Bioactive Molecules: Exports and Functionsmentioning

confidence: 99%

Perils and Promises of Pathogenic Protozoan Extracellular Vesicles

Olajide

Cai

2020

Front. Cell. Infect. Microbiol.

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Extracellular vesicles (EVs) are membranous structures formed during biological processes in living organisms. For protozoan parasites, secretion of EVs can occur directly from the parasite organellar compartments and through parasite-infected or antigen-stimulated host cells in response to in vitro and in vivo physiological stressors. These secreted EVs characteristically reflect the biochemical features of their parasitic origin and activating stimuli. Here, we review the species-specific morphology and integrity of parasitic protozoan EVs in concurrence with the origin, functions, and internalization process by recipient cells. The activating stimuli for the secretion of EVs in pathogenic protozoa are discoursed alongside their biomolecules and specific immune cell responses to protozoan parasite-derived EVs. We also present some insights on the intricate functions of EVs in the context of protozoan parasitism.

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Malaria Parasites Distribute Subversive Messages across Enemy Lines

Cited by 5 publications

References 10 publications

Malaria parasite DNA-harbouring vesicles activate cytosolic immune sensors

Malaria parasite DNA-harbouring vesicles activate cytosolic immune sensors

Plasmodium knowlesi:a superbin vivononhuman primate model of antigenic variation in malaria

Perils and Promises of Pathogenic Protozoan Extracellular Vesicles

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