Surface molecules of extracellular vesicles secreted by the helminth pathogen Fasciola hepatica direct their internalisation by host cells.
Helminth parasites secrete extracellular vesicles (EVs) that can be internalised by host immune cells resulting in modulation of host immunity. While the molecular cargo of EVs have been characterised in many parasites, little is known about the surface-exposed molecules that participate in ligand-r...
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ftdoajarticles:oai:doaj.org/article:9bdc6ecfce04429f878cefd3239720d4 2023-05-15T15:15:58+02:00 Surface molecules of extracellular vesicles secreted by the helminth pathogen Fasciola hepatica direct their internalisation by host cells. Eduardo de la Torre-Escudero Jared Q Gerlach Adam P S Bennett Krystyna Cwiklinski Heather L Jewhurst Kathryn M Huson Lokesh Joshi Michelle Kilcoyne Sandra O'Neill John P Dalton Mark W Robinson 2019-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0007087 https://doaj.org/article/9bdc6ecfce04429f878cefd3239720d4 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC6355031?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0007087 https://doaj.org/article/9bdc6ecfce04429f878cefd3239720d4 PLoS Neglected Tropical Diseases, Vol 13, Iss 1, p e0007087 (2019) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2019 ftdoajarticles https://doi.org/10.1371/journal.pntd.0007087 2023-01-08T01:25:30Z Helminth parasites secrete extracellular vesicles (EVs) that can be internalised by host immune cells resulting in modulation of host immunity. While the molecular cargo of EVs have been characterised in many parasites, little is known about the surface-exposed molecules that participate in ligand-receptor interactions with the host cell surface to initiate vesicle docking and subsequent internalisation. Using a membrane-impermeable biotin reagent to capture proteins displayed on the outer membrane surface of two EV sub-populations (termed 15k and 120k EVs) released by adult F. hepatica, we describe 380 surface proteins including an array of virulence factors, membrane transport proteins and molecules involved in EV biogenesis/trafficking. Proteomics and immunohistochemical analysis show that the 120k EVs have an endosomal origin and may be released from the parasite via the protonephridial (excretory) system whilst the larger 15k EVs are released from the gastrodermal epithelial cells that line the fluke gut. A parallel lectin microarray strategy was used to profile the topology of major surface oligosaccharides of intact fluorogenically-labelled EVs as they would be displayed to the host. Lectin profiles corresponding to glycoconjugates exposed on the surface of the 15 K and 120K EV sub-populations are practically identical but are distinct from those of the parasite surface tegument, although all are predominated by high mannose sugars. We found that while the F. hepatica EVs were resistant to exo- and endo-glycosidases, the glyco-amidase PNGase F drastically remodelled the surface oligosaccharides and blocked the uptake of EVs by host macrophages. In contrast, pre-treatment with antibodies obtained from infected hosts, or purified antibodies raised against the extracellular domains of specific EV surface proteins (DM9-containing protein, CD63 receptor and myoferlin), significantly enhanced their cellular internalisation. This work highlights the diversity of EV biogenesis and trafficking pathways used by F. ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 13 1 e0007087 |
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Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Eduardo de la Torre-Escudero Jared Q Gerlach Adam P S Bennett Krystyna Cwiklinski Heather L Jewhurst Kathryn M Huson Lokesh Joshi Michelle Kilcoyne Sandra O'Neill John P Dalton Mark W Robinson Surface molecules of extracellular vesicles secreted by the helminth pathogen Fasciola hepatica direct their internalisation by host cells. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Helminth parasites secrete extracellular vesicles (EVs) that can be internalised by host immune cells resulting in modulation of host immunity. While the molecular cargo of EVs have been characterised in many parasites, little is known about the surface-exposed molecules that participate in ligand-receptor interactions with the host cell surface to initiate vesicle docking and subsequent internalisation. Using a membrane-impermeable biotin reagent to capture proteins displayed on the outer membrane surface of two EV sub-populations (termed 15k and 120k EVs) released by adult F. hepatica, we describe 380 surface proteins including an array of virulence factors, membrane transport proteins and molecules involved in EV biogenesis/trafficking. Proteomics and immunohistochemical analysis show that the 120k EVs have an endosomal origin and may be released from the parasite via the protonephridial (excretory) system whilst the larger 15k EVs are released from the gastrodermal epithelial cells that line the fluke gut. A parallel lectin microarray strategy was used to profile the topology of major surface oligosaccharides of intact fluorogenically-labelled EVs as they would be displayed to the host. Lectin profiles corresponding to glycoconjugates exposed on the surface of the 15 K and 120K EV sub-populations are practically identical but are distinct from those of the parasite surface tegument, although all are predominated by high mannose sugars. We found that while the F. hepatica EVs were resistant to exo- and endo-glycosidases, the glyco-amidase PNGase F drastically remodelled the surface oligosaccharides and blocked the uptake of EVs by host macrophages. In contrast, pre-treatment with antibodies obtained from infected hosts, or purified antibodies raised against the extracellular domains of specific EV surface proteins (DM9-containing protein, CD63 receptor and myoferlin), significantly enhanced their cellular internalisation. This work highlights the diversity of EV biogenesis and trafficking pathways used by F. ... |
format |
Article in Journal/Newspaper |
author |
Eduardo de la Torre-Escudero Jared Q Gerlach Adam P S Bennett Krystyna Cwiklinski Heather L Jewhurst Kathryn M Huson Lokesh Joshi Michelle Kilcoyne Sandra O'Neill John P Dalton Mark W Robinson |
author_facet |
Eduardo de la Torre-Escudero Jared Q Gerlach Adam P S Bennett Krystyna Cwiklinski Heather L Jewhurst Kathryn M Huson Lokesh Joshi Michelle Kilcoyne Sandra O'Neill John P Dalton Mark W Robinson |
author_sort |
Eduardo de la Torre-Escudero |
title |
Surface molecules of extracellular vesicles secreted by the helminth pathogen Fasciola hepatica direct their internalisation by host cells. |
title_short |
Surface molecules of extracellular vesicles secreted by the helminth pathogen Fasciola hepatica direct their internalisation by host cells. |
title_full |
Surface molecules of extracellular vesicles secreted by the helminth pathogen Fasciola hepatica direct their internalisation by host cells. |
title_fullStr |
Surface molecules of extracellular vesicles secreted by the helminth pathogen Fasciola hepatica direct their internalisation by host cells. |
title_full_unstemmed |
Surface molecules of extracellular vesicles secreted by the helminth pathogen Fasciola hepatica direct their internalisation by host cells. |
title_sort |
surface molecules of extracellular vesicles secreted by the helminth pathogen fasciola hepatica direct their internalisation by host cells. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2019 |
url |
https://doi.org/10.1371/journal.pntd.0007087 https://doaj.org/article/9bdc6ecfce04429f878cefd3239720d4 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 13, Iss 1, p e0007087 (2019) |
op_relation |
http://europepmc.org/articles/PMC6355031?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0007087 https://doaj.org/article/9bdc6ecfce04429f878cefd3239720d4 |
op_doi |
https://doi.org/10.1371/journal.pntd.0007087 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
13 |
container_issue |
1 |
container_start_page |
e0007087 |
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1766346295275945984 |