Cargando…

Ivermectin inhibits extracellular vesicle secretion from parasitic nematodes

Lymphatic filariasis (LF) is a disease caused by parasitic filarial nematodes that is endemic in 49 countries of the world 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 la...

Descripción completa

Detalles Bibliográficos
Autores principales: Loghry, Hannah J., Yuan, Wang, Zamanian, Mostafa, Wheeler, Nicolas J., Day, Timothy A., Kimber, Michael J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726798/
https://www.ncbi.nlm.nih.gov/pubmed/33318780
http://dx.doi.org/10.1002/jev2.12036
_version_ 1783620957490905088
author Loghry, Hannah J.
Yuan, Wang
Zamanian, Mostafa
Wheeler, Nicolas J.
Day, Timothy A.
Kimber, Michael J.
author_facet Loghry, Hannah J.
Yuan, Wang
Zamanian, Mostafa
Wheeler, Nicolas J.
Day, Timothy A.
Kimber, Michael J.
author_sort Loghry, Hannah J.
collection PubMed
description Lymphatic filariasis (LF) is a disease caused by parasitic filarial nematodes that is endemic in 49 countries of the world 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.
format Online
Article
Text
id pubmed-7726798
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-77267982020-12-13 Ivermectin inhibits extracellular vesicle secretion from parasitic nematodes Loghry, Hannah J. Yuan, Wang Zamanian, Mostafa Wheeler, Nicolas J. Day, Timothy A. Kimber, Michael J. J Extracell Vesicles Research Articles Lymphatic filariasis (LF) is a disease caused by parasitic filarial nematodes that is endemic in 49 countries of the world 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. John Wiley and Sons Inc. 2020-12-10 2020-12 /pmc/articles/PMC7726798/ /pubmed/33318780 http://dx.doi.org/10.1002/jev2.12036 Text en © 2020 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Loghry, Hannah J.
Yuan, Wang
Zamanian, Mostafa
Wheeler, Nicolas J.
Day, Timothy A.
Kimber, Michael J.
Ivermectin inhibits extracellular vesicle secretion from parasitic nematodes
title Ivermectin inhibits extracellular vesicle secretion from parasitic nematodes
title_full Ivermectin inhibits extracellular vesicle secretion from parasitic nematodes
title_fullStr Ivermectin inhibits extracellular vesicle secretion from parasitic nematodes
title_full_unstemmed Ivermectin inhibits extracellular vesicle secretion from parasitic nematodes
title_short Ivermectin inhibits extracellular vesicle secretion from parasitic nematodes
title_sort ivermectin inhibits extracellular vesicle secretion from parasitic nematodes
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726798/
https://www.ncbi.nlm.nih.gov/pubmed/33318780
http://dx.doi.org/10.1002/jev2.12036
work_keys_str_mv AT loghryhannahj ivermectininhibitsextracellularvesiclesecretionfromparasiticnematodes
AT yuanwang ivermectininhibitsextracellularvesiclesecretionfromparasiticnematodes
AT zamanianmostafa ivermectininhibitsextracellularvesiclesecretionfromparasiticnematodes
AT wheelernicolasj ivermectininhibitsextracellularvesiclesecretionfromparasiticnematodes
AT daytimothya ivermectininhibitsextracellularvesiclesecretionfromparasiticnematodes
AT kimbermichaelj ivermectininhibitsextracellularvesiclesecretionfromparasiticnematodes