Schistosomal miRNAs isolated from Extracellular Vesicles in sera of infected patients; a new tool for diagnosis and follow-up of human schistosomiasis

Meningher, Tal; Lerman, Galya; Regev‐Rudzki, Neta; Gold, Daniel; Ben‐Dov, Iddo Z.; Sidi, Yechezkel; Avni, Dror; Schwartz, Eli

doi:10.1093/infdis/jiw539

Cited by 50 publications

(65 citation statements)

References 37 publications

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“…These results demonstrate an association between the schistosomal miRNAs and the EV fraction. These results are consistent with our previous data demonstrating schistosomal miRNAs in the fraction of EVs that were isolated from the sera of Schistosoma-infected patients [63]. In parallel, schistosomal-growth medium (used supernatant) was filtered through 0.1-lm membrane to deplete schistosomal EVs and placed on top of a trans-well above Th cells.…”

Section: Schistosomal-ev-enclosed Mirnas Penetrate Schistosomalexposesupporting

confidence: 92%

“…To further assess whether miRNAs were transferred by these EVs, the schistosomal EVs or the control pellets were added to the Jurkat cells. Forty-eight hours later, the RNA was extracted and subjected to qRT-PCR using the one-step real-time RT-PCR protocol that allows detection of very low amount of miRNAs [63]. The schistosomal miRNAs miR-125 and Bantam were detected in schistosomal-EV-exposed Jurkat cells but not in the control (Appendix Fig S4).…”

Section: Map3k7 (Tak1) Is a Target Of Schistosomal Mir-10mentioning

confidence: 99%

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Schistosomal extracellular vesicle‐enclosed miRNAs modulate host T helper cell differentiation

et al. 2019

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During the chronic stage of Schistosoma infection, the female lays fertile eggs, triggering a strong anti-parasitic type 2 helper T-cell (Th2) immune response. It is unclear how this Th2 response gradually declines even though the worms live for years and continue to produce eggs. Here, we show that Schistosoma mansoni downregulates Th2 differentiation in an antigen-presenting cell-independent manner, by modulating the Th2-specific transcriptional program. Adult schistosomes secrete miRNA-harboring extracellular vesicles that are internalized by Th cells in vitro. Schistosomal miRNAs are found also in T helper cells isolated from Peyer's patches and mesenteric lymph nodes of infected mice. In T helper cells, the schistosomal miR-10 targets MAP3K7 and consequently downmodulates NF-jB activity, a critical transcription factor for Th2 differentiation and function. Our results explain, at least partially, how schistosomes tune down the Th2 response, and provide further insight into the reciprocal geographic distribution between high prevalence of parasitic infections and immune disorders such as allergy. Furthermore, this worm-host crosstalk mechanism can be harnessed to develop diagnostic and therapeutic approaches for human schistosomiasis and Th2-associated diseases.

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Section: Schistosomal-ev-enclosed Mirnas Penetrate Schistosomalexposesupporting

confidence: 92%

Section: Map3k7 (Tak1) Is a Target Of Schistosomal Mir-10mentioning

confidence: 99%

Schistosomal extracellular vesicle‐enclosed miRNAs modulate host T helper cell differentiation

et al. 2019

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“…32 Another factor that needs to be considered when selecting EVs isolation protocols across different biofluids is the volume of starting material, as some biofluids may need to be concentrated prior to EVs isolation such as urine, an important source for patients diagnosed with renal pathologies, prostate and bladder cancers, 18 and other conditions including the parasitic infection schistosomiasis. 34 A recent study compared several filters and concluded that the best for recovering EVs from plasma, urine and EV-spiked PBS was a regenerated cellulose membrane with pores capable of retaining particles above 10 kDa. 35 Liang et al, have also demonstrated the feasibility of concentrating the EVs using a double-filtration microfluidic device capable of isolating, concentrating and quantifying urinary EVs, using 8 mL of the pre-filtered (0.22 μm filter) and 20 000g centrifuged urine-supernatant collected from bladder cancer patients and controls.…”

Section: Reviewmentioning

confidence: 99%

Technical challenges of working with extracellular vesicles

et al. 2018

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Extracellular Vesicles (EVs) are gaining interest as central players in liquid biopsies, with potential applications in diagnosis, prognosis and therapeutic guidance in most pathological conditions. These nanosized particles transmit signals determined by their protein, lipid, nucleic acid and sugar content, and the unique molecular pattern of EVs dictates the type of signal to be transmitted to recipient cells. However, their small sizes and the limited quantities that can usually be obtained from patient-derived samples pose a number of challenges to their isolation, study and characterization. These challenges and some possible options to overcome them are discussed in this review.

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“…Circulating miRNAs have been studied and proposed as diagnostic biomarkers in many infectious diseases including malaria. Most studies on infectious diseases have detected human miRNAs such as those in tuberculosis [81], hepatitis B [82], schistosomiasis [83] while some studies investigated microbial miRNAs as biomarkers as well [57,[84][85][86]. Despite the fact that Plasmodium spp.…”

Section: Discussionmentioning

confidence: 99%

“…Hypergeometric distribution) was applied for enrichment analysis. The potential pathways were considered based on their p-value (p<0.05).Evaluation of potential EVs-derived miRNA as biomarkerMean of Delta Cq for each miRNA was used in this analysis following the previous study[57]. The Receiver Operating Characteristic (ROC) was calculated to propose the potential use of miRNAs as diagnostic tools.…”

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The characterization of extracellular vesicles-derived microRNAs in Thai malaria patients

Ketprasit

Cheng

Deutsch

et al. 2020

Preprint

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Background Extracellular vesicles (EVs) have been broadly studied in malaria for nearly a decade. These vesicles carry various functional biomolecules including RNA families such as microRNAs (miRNA). These EVs-derived microRNAs have numerous roles in host-parasite interactions and are considered as promising biomarkers for disease severity. However, this field lacks clinical studies of malaria-infected samples. In our study, we investigated EV specific miRNAs isolated from the plasma of patients from Thailand infected with Plasmodium falciparum and Plasmodium vivax . We postulated that these miRNAs were differentially expressed in these groups of patients and had a role in disease onset through the regulation of specific target genes. Methods EVs were purified from the plasma of Thai P.vivax -infected patients (PV, n=19), P.falciparum -infected patients (PF, n=18) and uninfected individuals (n=20). EV-derived miRNAs were then prepared and abundance of miR-15b-5p, hsa-miR-16-5p, hsa-let-7a-5p and hsa-miR-150-5p was assessed in these samples. Quantitative Polymerase Chain Reaction was performed, and relative expression of each miRNA was calculated using hsa-miR-451a as endogenous control. We then predicted the targets of up-regulated miRNAs and relevant pathways by bioinformatics. Receiver Operating Characteristic with Area Under the Curve (AUC) was then calculated to assess their diagnostic potential. Results The relative expression of hsa-miR-150-5p and hsa-miR-15b-5p was higher in PV patients compared to uninfected individuals, but hsa-let-7a-5p was up-regulated in both PV and PF. Bioinformatic analysis revealed that these miRNAs might regulate genes involved in the malaria pathway including the Adherens junction and the transforming growth factor-β pathways. All up-regulated miRNAs could potentially be used as disease biomarker as determined by AUC; however, the sensitivity and specificity require further investigation. Conclusion The up-regulated hsa-miR-150-5p and hsa-miR-15b-5p in PV, hsa-let-7a-5p in both PV and PF may play a role in host-parasite interactions. The findings in this study will require further validation in larger cohort groups of malaria patients to fully understand the contribution of these EV miRNAs to malaria detection and biology.

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Schistosomal miRNAs isolated from Extracellular Vesicles in sera of infected patients; a new tool for diagnosis and follow-up of human schistosomiasis

Cited by 50 publications

References 37 publications

Schistosomal extracellular vesicle‐enclosed miRNAs modulate host T helper cell differentiation

Schistosomal extracellular vesicle‐enclosed miRNAs modulate host T helper cell differentiation

Technical challenges of working with extracellular vesicles

The characterization of extracellular vesicles-derived microRNAs in Thai malaria patients

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