A preliminary proteomic characterisation of extracellular vesicles released by the ovine parasitic nematode, Teladorsagia circumcincta

Tzelos, Thomas; Matthews, J. B.; Buck, Amy H.; Simbari, Fabio; Frew, David; Inglis, Neil F.; McLean, Kevin; Nisbet, Alasdair J.; Whitelaw, Bruce; Knox, David P.; McNeilly, Tom N.

doi:10.1016/j.vetpar.2016.03.008

Cited by 49 publications

(56 citation statements)

References 88 publications

(142 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Helminth EVs were first described in the free‐living nematode Caenorhabdidits elegans and were attributed functions in communication and mating‐related behaviors . More recently, a steady stream of publications have described the secretion of EVs from parasitic helminths, including liver‐ and blood flukes ( Fasciola hepatica, Echinostoma caproni, Dicrocoelium dendriticum, Opisthorchis viverrini, Schistosoma mansoni and Schistosoma japonicum ), roundworm nematodes ( Heligmosomoides polygyrus, Trichuris suis, Trichuris muris, Teladorsagia circumcincta, Brugia malayi , Dirofilaria immitis and Nippostrongylus brasiliensis ) and tapeworm cestodes ( Echinococcus multilocularis , Echinococcus granulosus , Taenia crassiceps and Mesocestoides corti ) …”

Section: Effects Of Helminth Evs On the Host Immune Systemmentioning

confidence: 99%

See 1 more Smart Citation

Immunobiology of parasitic worm extracellular vesicles

2018

View full text Add to dashboard Cite

Helminth parasites (worms) have evolved a vast array of strategies to manipulate their vertebrate hosts. Extracellular vesicles (EVs) are secreted by all helminth species investigated thus far, and their salient roles in parasite-host interactions are being revealed. Parasite EVs directly interact with various cell types from their hosts, including immune cells, and roles for their molecular cargo in both regulation and promotion of inflammation in the host have been reported. Despite the growing body of literature on helminth EVs, limited availability of genetic manipulation tools for helminth research has precluded detailed investigation of specific molecular interactions between parasite EVs and host target cells. Here, we review the current state of the field and discuss innovative strategies targeting helminth EVs for the discovery and development of new therapeutic strategies, placing particular emphasis on both anti-helminth vaccines and EV small RNAs for treating noninfectious inflammatory diseases.

show abstract

Section: Effects Of Helminth Evs On the Host Immune Systemmentioning

confidence: 99%

“…Nevertheless, macrophage proliferation and expression of some surface molecules (CD11, CD80 and MHC II) are not affected . Similarly, cathepsin F, which was found in EVs from T. circumcincta , has been suggested to suppress Th1 responses by suppressing IFN‐γ production …”

Section: Specific Ev Cargo With Proposed Immunomodulatory Propertiesmentioning

confidence: 99%

Immunobiology of parasitic worm extracellular vesicles

2018

View full text Add to dashboard Cite

show abstract

“…Consistent with a role in cell-to-cell communication, EVs contain diverse functional cargo that varies depending on the cellular origin of the EVs, but in general include bioactive proteins, RNA and lipids (Thery et al, 2002;Valadi et al, 2007). EV secretion from diverse parasitic nematodes has been described (Buck et al, 2014;Coakley et al, 2017;Eichenberger, Ryan, et al, 2018;Eichenberger, Talukder, et al, 2018;Gu et al, 2017;Hansen et al, 2015Hansen et al, , 2019Harischandra et al, 2018;Shears et al, 2018;Tritten et al, 2017;Tzelos et al, 2016;Zamanian et al, 2015) and the cargo of these EVs have immunomodulatory functions (Buck et al, 2014;Quintana et al, 2017;Tritten et al, 2016). We have previously reported that B. malayi secretes EVs and that their cargo has putative immunomodulatory properties (Harischandra et al, 2018;Zamanian et al, 2015).…”

Section: Introductionmentioning

confidence: 89%

Ivermectin inhibits extracellular vesicle secretion from parasitic nematodes

Loghry

Wang

Zamanian

et al. 2020

Preprint

View full text Add to dashboard Cite

Lymphatic filariasis (LF) is a disease caused by parasitic filarial nematodes that is endemic in 49 countries and affects or threatens over 890 million people. Strategies to control LF rely heavily on mass administration of anthelmintic drugs including ivermectin (IVM), a macrocyclic lactone drug considered an Essential Medicine by the WHO. However, despite its widespread use the therapeutic mode of action of IVM against filarial nematodes is not clear. We have previously reported that filarial nematodes secrete extracellular vesicles (EVs) and that their cargo has immunomodulatory properties. Here we investigate the effects of IVM and other anti-filarial drugs on parasitic nematode EV secretion, motility, and protein secretion. We show that inhibition of EV secretion was a specific property of IVM, which had consistent and significant inhibitory effects across nematode life stages and species (with the exception of male parasites). IVM inhibited EV secretion, but not parasite motility, at therapeutically relevant concentrations. Protein secretion was inhibited by IVM in the microfilariae stage, but not in any other stage tested. Our data provides evidence that inhibiting the secretion of immunomodulatory EVs by parasitic nematodes could explain, at least in part, IVM mode of action and provides a phenotype for novel drug discovery.

show abstract

“…Initial reports in the trematodes Echinostoma caproni and Fasciola hepatica suggested that EVs (30‐100 nm) could derive from tegumental structures and could be a mechanism for transferring material to host cells . EVs with similar sizes have also been characterized in the human pathogenic trematodes Schistosoma mansoni and Schistosoma japonicum, the carcinogenic liver fluke Opisthorchis viverrini, the clade V gastrointestinal nematode Teladorsagia circumcincta and the clade I whipworm Trichuris suis . In our own work, we showed that the clade V gastrointestinal parasitic nematode H. polygyrus secretes EVs that are enriched in proteins known to be abundant in the intestinal tissue of the parasite as well proteins associated with exosome biogenesis (e.g.…”

Section: Extracellular Vesicles and Extracellular Rna In Filarial Nemmentioning

confidence: 99%

Small RNAs and extracellular vesicles in filarial nematodes: From nematode development to diagnostics

Quintana

Babayan

Buck

2017

Parasite Immunology

View full text Add to dashboard Cite

SummaryParasitic nematodes have evolved sophisticated mechanisms to communicate with their hosts in order to survive and successfully establish an infection. The transfer of RNA within extracellular vesicles (EVs) has recently been described as a mechanism that could contribute to this communication in filarial nematodes. It has been shown that these EVs are loaded with several types of RNAs, including microRNAs, leading to the hypothesis that parasites could actively use these molecules to manipulate host gene expression and to the exciting prospect that these pathways could result in new diagnostic and therapeutic strategies. Here, we review the literature on the diverse RNAi pathways that operate in nematodes and more specifically our current knowledge of extracellular RNA (exRNA) and EVs derived from filarial nematodes in vitro and within their hosts. We further detail some of the issues and questions related to the capacity of RNA-mediated communication to function in parasite-host interactions and the ability of exRNA to enable us to distinguish and detect different nematode parasites in their hosts.

show abstract

A preliminary proteomic characterisation of extracellular vesicles released by the ovine parasitic nematode, Teladorsagia circumcincta

Abstract: Graphical abstract

Cited by 49 publications

References 88 publications

Immunobiology of parasitic worm extracellular vesicles

Immunobiology of parasitic worm extracellular vesicles

Ivermectin inhibits extracellular vesicle secretion from parasitic nematodes

Small RNAs and extracellular vesicles in filarial nematodes: From nematode development to diagnostics

Contact Info

Product

Resources

About