Conservation of a microRNA cluster in parasitic nematodes and profiling of miRNAs in excretory-secretory products and microvesicles of Haemonchus contortus

Gu, Henry Y.; Marks, Neil D.; Winter, Alan D.; Weir, William; Tzelos, Thomas; McNeilly, Tom N.; Britton, Collette; Devaney, Eileen

doi:10.1371/journal.pntd.0006056

Cited by 41 publications

(38 citation statements)

References 28 publications

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“…Gu et al also suggest that some helminth miRNAs only might target host genes and that their release is a selective process as the profile of released miRNAs in the excretory-secretory products differed from that of adult extracts of Haemonchus contortus ( 227 ).…”

Section: Evs For the Host Immune Systemmentioning

confidence: 99%

Immunomodulation by Helminths: Intracellular Pathways and Extracellular Vesicles

et al. 2018

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Helminth parasites are masters at manipulating host immune responses, using an array of sophisticated mechanisms. One of the major mechanisms enabling helminths to establish chronic infections is the targeting of pattern recognition receptors (PRRs) including toll-like receptors, C-type lectin receptors, and the inflammasome. Given the critical role of these receptors and their intracellular pathways in regulating innate inflammatory responses, and also directing adaptive immunity toward Th1 and Th2 responses, recognition of the pathways triggered and/or modulated by helminths and their products will provide detailed insights about how helminths are able to establish an immunoregulatory environment. However, helminths also target PRRs-independent mechanisms (and most likely other yet unknown mechanisms and pathways) underpinning the battery of different molecules helminths produce. Herein, the current knowledge on intracellular pathways in antigen presenting cells activated by helminth-derived biomolecules is reviewed. Furthermore, we discuss the importance of helminth-derived vesicles as a less-appreciated components released during infection, their role in activating these host intracellular pathways, and their implication in the development of new therapeutic approaches for inflammatory diseases and the possibility of designing a new generation of vaccines.

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Section: Evs For the Host Immune Systemmentioning

confidence: 99%

Immunomodulation by Helminths: Intracellular Pathways and Extracellular Vesicles

et al. 2018

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“…In contrast to miRNAs and siRNAs, processing does not depend in Dicer ribonuclease. Following the generation of initial primary piRNAs, sequences targeting active transposons are amplified by slicing of the target RNA to give rise to secondary piRNAs (referred to as the ping-pong cycle) (Gunawardane et al, 2007). It is thought that this amplification fine-tunes the piRNA response against active transposons (reviewed in Siomi et al, 2011).…”

Section: Identification Of Pirnasmentioning

confidence: 99%

Small RNAs in parasitic nematodes – forms and functions

2019

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Small RNAs are important regulators of gene expression. They were first identified in Caenorhabditis elegans, but it is now apparent that the main small RNA silencing pathways are functionally conserved across diverse organisms. Availability of genome data for an increasing number of parasitic nematodes has enabled bioinformatic identification of small RNA sequences. Expression of these in different lifecycle stages is revealed by small RNA sequencing and microarray analysis. In this review we describe what is known of the three main small RNA classes in parasitic nematodes – microRNAs (miRNAs), Piwi-interacting RNAs (piRNAs) and small interfering RNAs (siRNAs) – and their proposed functions. miRNAs regulate development in C. elegans and the temporal expression of parasitic nematode miRNAs suggest modulation of target gene levels as parasites develop within the host. miRNAs are also present in extracellular vesicles released by nematodes in vitro, and in plasma from infected hosts, suggesting potential regulation of host gene expression. Roles of piRNAs and siRNAs in suppressing target genes, including transposable elements, are also reviewed. Recent successes in RNAi-mediated gene silencing, and application of small RNA inhibitors and mimics will continue to advance understanding of small RNA functions within the parasite and at the host–parasite interface.

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“…The recognition that exosomes are important mediators of cell-to-cell communication [ 23 , 24 ] has triggered an explosion of interest in EV biology, attributing functions to EV in an array of non-communicable and infectious diseases, whilst recognizing their diagnostic and therapeutic potential [ 25 – 28 ]. The idea that parasitic helminths secrete EV and that these vesicles function at the host parasite interface is an emerging concept with EV release from both nematode [ 29 – 33 ] and platyhelminth species [ 34 – 39 ] recently documented. We have shown that infectious L3 stage B .…”

Section: Introductionmentioning

confidence: 99%

Profiling extracellular vesicle release by the filarial nematode Brugia malayi reveals sex-specific differences in cargo and a sensitivity to ivermectin

et al. 2018

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The filarial nematode Brugia malayi is an etiological agent of Lymphatic Filariasis. The capability of B. malayi and other parasitic nematodes to modulate host biology is recognized but the mechanisms by which such manipulation occurs are obscure. An emerging paradigm is the release of parasite-derived extracellular vesicles (EV) containing bioactive proteins and small RNA species that allow secretion of parasite effector molecules and their potential trafficking to host tissues. We have previously described EV release from the infectious L3 stage B. malayi and here we profile vesicle release across all intra-mammalian life cycle stages (microfilariae, L3, L4, adult male and female worms). Nanoparticle Tracking Analysis was used to quantify and size EVs revealing discrete vesicle populations and indicating a secretory process that is conserved across the life cycle. Brugia EVs are internalized by murine macrophages with no preference for life stage suggesting a uniform mechanism for effector molecule trafficking. Further, the use of chemical uptake inhibitors suggests all life stage EVs are internalized by phagocytosis. Proteomic profiling of adult male and female EVs using nano-scale LC-MS/MS described quantitative and qualitative differences in the adult EV proteome, helping define the biogenesis of Brugia EVs and revealing sexual dimorphic characteristics in immunomodulatory cargo. Finally, ivermectin was found to rapidly inhibit EV release by all Brugia life stages. Further this drug effect was also observed in the related filarial nematode, the canine heartworm Dirofilaria immitis but not in an ivermectin-unresponsive field isolate of that parasite, highlighting a potential mechanism of action for this drug and suggesting new screening platforms for anti-filarial drug development.

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Conservation of a microRNA cluster in parasitic nematodes and profiling of miRNAs in excretory-secretory products and microvesicles of Haemonchus contortus

Cited by 41 publications

References 28 publications

Immunomodulation by Helminths: Intracellular Pathways and Extracellular Vesicles

Immunomodulation by Helminths: Intracellular Pathways and Extracellular Vesicles

Small RNAs in parasitic nematodes – forms and functions

Profiling extracellular vesicle release by the filarial nematode Brugia malayi reveals sex-specific differences in cargo and a sensitivity to ivermectin

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