Cargando…

Characterisation of a niche-specific excretory–secretory peroxiredoxin from the parasitic nematode Teladorsagia circumcincta

BACKGROUND: The primary cause of parasitic gastroenteritis in small ruminants in temperate regions is the brown stomach worm, Teladorsagia circumcincta. Host immunity to this parasite is slow to develop, consistent with the ability of T. circumcincta to suppress the host immune response. Previous st...

Descripción completa

Detalles Bibliográficos
Autores principales: Price, Daniel R. G., Nisbet, Alasdair J., Frew, David, Bartley, Yvonne, Oliver, E. Margaret, McLean, Kevin, Inglis, Neil F., Watson, Eleanor, Corripio-Miyar, Yolanda, McNeilly, Tom N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6617597/
https://www.ncbi.nlm.nih.gov/pubmed/31292008
http://dx.doi.org/10.1186/s13071-019-3593-6
_version_ 1783433726766612480
author Price, Daniel R. G.
Nisbet, Alasdair J.
Frew, David
Bartley, Yvonne
Oliver, E. Margaret
McLean, Kevin
Inglis, Neil F.
Watson, Eleanor
Corripio-Miyar, Yolanda
McNeilly, Tom N.
author_facet Price, Daniel R. G.
Nisbet, Alasdair J.
Frew, David
Bartley, Yvonne
Oliver, E. Margaret
McLean, Kevin
Inglis, Neil F.
Watson, Eleanor
Corripio-Miyar, Yolanda
McNeilly, Tom N.
author_sort Price, Daniel R. G.
collection PubMed
description BACKGROUND: The primary cause of parasitic gastroenteritis in small ruminants in temperate regions is the brown stomach worm, Teladorsagia circumcincta. Host immunity to this parasite is slow to develop, consistent with the ability of T. circumcincta to suppress the host immune response. Previous studies have shown that infective fourth-stage T. circumcincta larvae produce excretory–secretory products that are able to modulate the host immune response. The objective of this study was to identify immune modulatory excretory–secretory proteins from populations of fourth-stage T. circumcincta larvae present in two different host-niches: those associated with the gastric glands (mucosal-dwelling larvae) and those either loosely associated with the mucosa or free-living in the lumen (lumen-dwelling larvae). RESULTS: In this study excretory–secretory proteins from mucosal-dwelling and lumen-dwelling T. circumcincta fourth stage larvae were analysed using comparative 2-dimensional gel electrophoresis. A total of 17 proteins were identified as differentially expressed, with 14 proteins unique to, or enriched in, the excretory–secretory proteins of mucosal-dwelling larvae. One of the identified proteins, unique to mucosal-dwelling larvae, was a putative peroxiredoxin (T. circumcincta peroxiredoxin 1, Tci-Prx1). Peroxiredoxin orthologs from the trematode parasites Schistosoma mansoni and Fasciola hepatica have previously been shown to alternatively activate macrophages and play a key role in promoting parasite induced Th2 type immunity. Here we demonstrate that Tci-Prx1 is expressed in all infective T. circumcincta life-stages and, when produced as a recombinant protein, has peroxidase activity, whereby hydrogen peroxide (H(2)O(2)) is reduced and detoxified. Furthermore, we use an in vitro macrophage stimulation assay to demonstrate that, unlike peroxiredoxins from trematode parasites Schistosoma mansoni and Fasciola hepatica, Tci-Prx1 is unable to alternatively activate murine macrophage cells. CONCLUSIONS: In this study, we identified differences in the excretory–secretory proteome of mucosal-dwelling and lumen-dwelling infective fourth-stage T. circumcincta larvae, and demonstrated the utility of this comparative proteomic approach to identify excretory–secretory proteins of potential importance for parasite survival and/or host immune modulation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13071-019-3593-6) contains supplementary material, which is available to authorized users.
format Online
Article
Text
id pubmed-6617597
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-66175972019-07-18 Characterisation of a niche-specific excretory–secretory peroxiredoxin from the parasitic nematode Teladorsagia circumcincta Price, Daniel R. G. Nisbet, Alasdair J. Frew, David Bartley, Yvonne Oliver, E. Margaret McLean, Kevin Inglis, Neil F. Watson, Eleanor Corripio-Miyar, Yolanda McNeilly, Tom N. Parasit Vectors Research BACKGROUND: The primary cause of parasitic gastroenteritis in small ruminants in temperate regions is the brown stomach worm, Teladorsagia circumcincta. Host immunity to this parasite is slow to develop, consistent with the ability of T. circumcincta to suppress the host immune response. Previous studies have shown that infective fourth-stage T. circumcincta larvae produce excretory–secretory products that are able to modulate the host immune response. The objective of this study was to identify immune modulatory excretory–secretory proteins from populations of fourth-stage T. circumcincta larvae present in two different host-niches: those associated with the gastric glands (mucosal-dwelling larvae) and those either loosely associated with the mucosa or free-living in the lumen (lumen-dwelling larvae). RESULTS: In this study excretory–secretory proteins from mucosal-dwelling and lumen-dwelling T. circumcincta fourth stage larvae were analysed using comparative 2-dimensional gel electrophoresis. A total of 17 proteins were identified as differentially expressed, with 14 proteins unique to, or enriched in, the excretory–secretory proteins of mucosal-dwelling larvae. One of the identified proteins, unique to mucosal-dwelling larvae, was a putative peroxiredoxin (T. circumcincta peroxiredoxin 1, Tci-Prx1). Peroxiredoxin orthologs from the trematode parasites Schistosoma mansoni and Fasciola hepatica have previously been shown to alternatively activate macrophages and play a key role in promoting parasite induced Th2 type immunity. Here we demonstrate that Tci-Prx1 is expressed in all infective T. circumcincta life-stages and, when produced as a recombinant protein, has peroxidase activity, whereby hydrogen peroxide (H(2)O(2)) is reduced and detoxified. Furthermore, we use an in vitro macrophage stimulation assay to demonstrate that, unlike peroxiredoxins from trematode parasites Schistosoma mansoni and Fasciola hepatica, Tci-Prx1 is unable to alternatively activate murine macrophage cells. CONCLUSIONS: In this study, we identified differences in the excretory–secretory proteome of mucosal-dwelling and lumen-dwelling infective fourth-stage T. circumcincta larvae, and demonstrated the utility of this comparative proteomic approach to identify excretory–secretory proteins of potential importance for parasite survival and/or host immune modulation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13071-019-3593-6) contains supplementary material, which is available to authorized users. BioMed Central 2019-07-10 /pmc/articles/PMC6617597/ /pubmed/31292008 http://dx.doi.org/10.1186/s13071-019-3593-6 Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Price, Daniel R. G.
Nisbet, Alasdair J.
Frew, David
Bartley, Yvonne
Oliver, E. Margaret
McLean, Kevin
Inglis, Neil F.
Watson, Eleanor
Corripio-Miyar, Yolanda
McNeilly, Tom N.
Characterisation of a niche-specific excretory–secretory peroxiredoxin from the parasitic nematode Teladorsagia circumcincta
title Characterisation of a niche-specific excretory–secretory peroxiredoxin from the parasitic nematode Teladorsagia circumcincta
title_full Characterisation of a niche-specific excretory–secretory peroxiredoxin from the parasitic nematode Teladorsagia circumcincta
title_fullStr Characterisation of a niche-specific excretory–secretory peroxiredoxin from the parasitic nematode Teladorsagia circumcincta
title_full_unstemmed Characterisation of a niche-specific excretory–secretory peroxiredoxin from the parasitic nematode Teladorsagia circumcincta
title_short Characterisation of a niche-specific excretory–secretory peroxiredoxin from the parasitic nematode Teladorsagia circumcincta
title_sort characterisation of a niche-specific excretory–secretory peroxiredoxin from the parasitic nematode teladorsagia circumcincta
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6617597/
https://www.ncbi.nlm.nih.gov/pubmed/31292008
http://dx.doi.org/10.1186/s13071-019-3593-6
work_keys_str_mv AT pricedanielrg characterisationofanichespecificexcretorysecretoryperoxiredoxinfromtheparasiticnematodeteladorsagiacircumcincta
AT nisbetalasdairj characterisationofanichespecificexcretorysecretoryperoxiredoxinfromtheparasiticnematodeteladorsagiacircumcincta
AT frewdavid characterisationofanichespecificexcretorysecretoryperoxiredoxinfromtheparasiticnematodeteladorsagiacircumcincta
AT bartleyyvonne characterisationofanichespecificexcretorysecretoryperoxiredoxinfromtheparasiticnematodeteladorsagiacircumcincta
AT oliveremargaret characterisationofanichespecificexcretorysecretoryperoxiredoxinfromtheparasiticnematodeteladorsagiacircumcincta
AT mcleankevin characterisationofanichespecificexcretorysecretoryperoxiredoxinfromtheparasiticnematodeteladorsagiacircumcincta
AT inglisneilf characterisationofanichespecificexcretorysecretoryperoxiredoxinfromtheparasiticnematodeteladorsagiacircumcincta
AT watsoneleanor characterisationofanichespecificexcretorysecretoryperoxiredoxinfromtheparasiticnematodeteladorsagiacircumcincta
AT corripiomiyaryolanda characterisationofanichespecificexcretorysecretoryperoxiredoxinfromtheparasiticnematodeteladorsagiacircumcincta
AT mcneillytomn characterisationofanichespecificexcretorysecretoryperoxiredoxinfromtheparasiticnematodeteladorsagiacircumcincta