EV-transported microRNAs of Schistosoma mansoni and Fasciola hepatica: Potential targets in definitive hosts

Ovchinnikov, Vladimir; Кашина, Е. В.; Мордвинов, В. А.; Fromm, Bastian

doi:10.1016/j.meegid.2020.104528

Cited by 21 publications

(61 citation statements)

References 42 publications

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“…Of interest, miR-281, miR-279, miR-67, and miR-1993 identified in adult fluke by Fromm et al (39), are alternatively annotated as miR-46, miR-61, miR-307, and miR-2162 respectively, by Fontenla et al (40). An analysis of miR-281 and miR-46 showed that the sequences are in fact very similar, but have been classified as two distinct miRNAs in miRBase.…”

Section: An Evaluation Of the Fasciola Hepatica Mirnome Identified To Datementioning

confidence: 99%

“…Most recently, the small RNA sequencing data sets from the adult parasites (37) and their EVs (38) were re-evaluated again using an improved version of MirMiner (39). This study reported the discovery of four conserved miRNAs (Fhe-Let-7-P3, Fhe-Mir-133, Fhe-Mir-278 and Fhe-Mir-2160-P2) and four Fasciola-specific miRNAs.…”

Section: An Evaluation Of the Fasciola Hepatica Mirnome Identified To Datementioning

confidence: 99%

“…As this review was being finalized, a similar consideration of the biological role of the 46 of the most abundant miRNAs in adult parasites and EVs was published. Using a combination of TargetScan and PITA to predict gene targets within the genome of cattle and humans, and applying Reactome and KEGG pathway analysis to these targets, identified 44 and 23 genes respectively, that were characterized as having a role in the immune system (39).…”

Section: Predicted Gene Targets For Fasciola Hepatica Mirnas Reveal a High Degree Of Redundancy In The Regulation Of Immune Cell Activatimentioning

confidence: 99%

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An Evaluation of the Fasciola hepatica miRnome Predicts a Targeted Regulation of Mammalian Innate Immune Responses

et al. 2021

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Understanding mechanisms by which parasitic worms (helminths) control their hosts’ immune responses is critical to the development of effective new disease interventions. Fasciola hepatica, a global scourge of humans and their livestock, suppresses host innate immune responses within hours of infection, ensuring that host protective responses are quickly incapacitated. This allows the parasite to freely migrate from the intestine, through the liver to ultimately reside in the bile duct, where the parasite establishes a chronic infection that is largely tolerated by the host. The recent identification of micro(mi)RNA, small RNAs that regulate gene expression, within the extracellular vesicles secreted by helminths suggest that these non-coding RNAs may have a role in the parasite-host interplay. To date, 77 miRNAs have been identified in F. hepatica comprising primarily of ancient conserved species of miRNAs. We hypothesized that many of these miRNAs are utilized by the parasite to regulate host immune signaling pathways. To test this theory, we first compiled all of the known published F. hepatica miRNAs and critically curated their sequences and annotations. Then with a focus on the miRNAs expressed by the juvenile worms, we predicted gene targets within human innate immune cells. This approach revealed the existence of targets within every immune cell, providing evidence for the universal management of host immunology by this parasite. Notably, there was a high degree of redundancy in the potential for the parasite to regulate the activation of dendritic cells, eosinophils and neutrophils, with multiple miRNAs predicted to act on singular gene targets within these cells. This original exploration of the Fasciola miRnome offers the first molecular insight into mechanisms by which F. hepatica can regulate the host protective immune response.

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Section: An Evaluation Of the Fasciola Hepatica Mirnome Identified To Datementioning

confidence: 99%

Section: An Evaluation Of the Fasciola Hepatica Mirnome Identified To Datementioning

confidence: 99%

Section: Predicted Gene Targets For Fasciola Hepatica Mirnas Reveal a High Degree Of Redundancy In The Regulation Of Immune Cell Activatimentioning

confidence: 99%

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An Evaluation of the Fasciola hepatica miRnome Predicts a Targeted Regulation of Mammalian Innate Immune Responses

et al. 2021

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“…Ovchinnikov et al. analyzed the miRNAs from exosomes of S. mansoni adult female and male worms and predicted miRNA targets in human and cattle mRNAs ( 61 ). They found that in the hosts the Wnt pathway stood out as a primary target of S. mansoni RNAs; this evolutionarily conserved pathway participates in many biological processes including cell proliferation and liver physiology ( 62 ).…”

Section: Schistosome-derived Exosomes In Signal Transductionmentioning

confidence: 99%

“…They found that in the hosts the Wnt pathway stood out as a primary target of S. mansoni RNAs; this evolutionarily conserved pathway participates in many biological processes including cell proliferation and liver physiology ( 62 ). Several target genes from hosts involved in the immune system have also been identified, suppression of which could reduce inflammatory responses ( 61 ). Studies are ongoing to determine the precise signal transduction pathways activated in response to parasitic immune invasion.…”

Section: Schistosome-derived Exosomes In Signal Transductionmentioning

confidence: 99%

Understanding the Pathophysiology of Exosomes in Schistosomiasis: A New Direction for Disease Control and Prevention

et al. 2021

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Schistosomiasis is a parasitic disease endemic to freshwater areas of Southeast Asia, Africa, and South America that is capable of causing serious damage to the internal organs. Recent studies have linked exosomes to the progression of schistosomiasis. These structures are important mediators for intercellular communication, assist cells to exchange proteins, lipids, and genetic material and have been shown to play critical roles during host–parasite interactions. This review aims to discuss the pathophysiology of exosomes in schistosomiasis and their roles in regulating the host immune response. Understanding how exosomes are involved in the pathogenesis of schistosomiasis may provide new perspectives in diagnosing and treating this neglected disease.

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Extracellular vesicles from the trematodes Fasciola hepatica and Dicrocoelium dendriticum trigger different responses in human THP‐1 macrophages

Sánchez-López

González-Arce

Soler

et al. 2023

J of Extracellular Vesicle

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Extracellular vesicles (EVs) released by the helminths Dicrocoelium dendriticum and Fasciola hepatica are important modulators of the host immune response, contributing to the establishment of the infection. Monocytes and, in particular, macrophages are major regulators of the inflammatory response and are likely responsible for the phagocytosis of most of the parasite EVs. In this study, we isolated EVs from F. hepatica (FhEVs) and D. dendriticum (DdEVs) by size exclusion chromatography (SEC) and characterized them by nanoparticle tracking analysis, transmission electron microscopy and LC-MS/MS, and analyzed the cohort of proteins. The treatment of monocytes/macrophages with FhEVs, DdEVs or EV-depleted fractions from SEC, demonstrated species-specific effects of the EVs. In particular, FhEVs reduce the migratory capacity of monocytes and the analysis of the cytokine profile showed that they induce a mixed M1/M2 response, exerting anti-inflammatory properties in Lipopolysaccharide-activated macrophages. In contrast, DdEVs do not affect monocyte migration and seem to have pro-inflammatory properties. These results correlate with the differences in the life cycle of both parasites, suggesting different host immune responses. Only F. hepatica migrates to the bile duct through the liver parenchyma, driving the host immune response to heal deep erosions. Furthermore, the proteomic analysis of the macrophages upon FhEV treatment identified several proteins that might be involved in FhEV-macrophage interactions.

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EV-transported microRNAs of Schistosoma mansoni and Fasciola hepatica: Potential targets in definitive hosts

Cited by 21 publications

References 42 publications

An Evaluation of the Fasciola hepatica miRnome Predicts a Targeted Regulation of Mammalian Innate Immune Responses

An Evaluation of the Fasciola hepatica miRnome Predicts a Targeted Regulation of Mammalian Innate Immune Responses

Understanding the Pathophysiology of Exosomes in Schistosomiasis: A New Direction for Disease Control and Prevention

Extracellular vesicles from the trematodes Fasciola hepatica and Dicrocoelium dendriticum trigger different responses in human THP‐1 macrophages

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