Autonomous Non Antioxidant Roles for Fasciola hepatica Secreted Thioredoxin-1 and Peroxiredoxin-1
Trematode parasites of the genus Fasciola are the cause of liver fluke disease (fasciolosis) in humans and their livestock. Infection of the host involves invasion through the intestinal wall followed by migration in the liver that results in extensive damage, before the parasite settles as a mature...
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Frontiers Media S.A.
2021-05-01
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doaj-54f347db0562435db9ce1c0d052acc5b2021-05-05T05:15:26ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882021-05-011110.3389/fcimb.2021.667272667272Autonomous Non Antioxidant Roles for Fasciola hepatica Secreted Thioredoxin-1 and Peroxiredoxin-1Amber DoreyKrystyna CwiklinskiJames RooneyCarolina De Marco VerissimoJesús López CorralesHeather JewhurstBarbara FazekasNichola Eliza Davies CalvaniSiobhán HamonSiobhán GaughanJohn P. DaltonRichard LalorTrematode parasites of the genus Fasciola are the cause of liver fluke disease (fasciolosis) in humans and their livestock. Infection of the host involves invasion through the intestinal wall followed by migration in the liver that results in extensive damage, before the parasite settles as a mature egg-laying adult in the bile ducts. Genomic and transcriptomic studies revealed that increased metabolic stress during the rapid growth and development of F. hepatica is balanced with the up-regulation of the thiol-independent antioxidant system. In this cascade system thioredoxin/glutathione reductase (TGR) reduces thioredoxin (Trx), which then reduces and activates peroxiredoxin (Prx), whose major function is to protect cells against the damaging hydrogen peroxide free radicals. F. hepatica expresses a single TGR, three Trx and three Prx genes; however, the transcriptional expression of Trx1 and Prx1 far out-weighs (>50-fold) other members of their family, and both are major components of the parasite secretome. While Prx1 possesses a leader signal peptide that directs its secretion through the classical pathway and explains why this enzyme is found freely soluble in the secretome, Trx1 lacks a leader peptide and is secreted via an alternative pathway that packages the majority of this enzyme into extracellular vesicles (EVs). Here we propose that F. hepatica Prx1 and Trx1 do not function as part of the parasite’s stress-inducible thiol-dependant cascade, but play autonomous roles in defence against the general anti-pathogen oxidative burst by innate immune cells, in the modulation of host immune responses and regulation of inflammation.https://www.frontiersin.org/articles/10.3389/fcimb.2021.667272/fullFasciolahelminthantioxidantsthioredoxinthioredoxin peroxidaseperoxiredoxin |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Amber Dorey Krystyna Cwiklinski James Rooney Carolina De Marco Verissimo Jesús López Corrales Heather Jewhurst Barbara Fazekas Nichola Eliza Davies Calvani Siobhán Hamon Siobhán Gaughan John P. Dalton Richard Lalor |
spellingShingle |
Amber Dorey Krystyna Cwiklinski James Rooney Carolina De Marco Verissimo Jesús López Corrales Heather Jewhurst Barbara Fazekas Nichola Eliza Davies Calvani Siobhán Hamon Siobhán Gaughan John P. Dalton Richard Lalor Autonomous Non Antioxidant Roles for Fasciola hepatica Secreted Thioredoxin-1 and Peroxiredoxin-1 Frontiers in Cellular and Infection Microbiology Fasciola helminth antioxidants thioredoxin thioredoxin peroxidase peroxiredoxin |
author_facet |
Amber Dorey Krystyna Cwiklinski James Rooney Carolina De Marco Verissimo Jesús López Corrales Heather Jewhurst Barbara Fazekas Nichola Eliza Davies Calvani Siobhán Hamon Siobhán Gaughan John P. Dalton Richard Lalor |
author_sort |
Amber Dorey |
title |
Autonomous Non Antioxidant Roles for Fasciola hepatica Secreted Thioredoxin-1 and Peroxiredoxin-1 |
title_short |
Autonomous Non Antioxidant Roles for Fasciola hepatica Secreted Thioredoxin-1 and Peroxiredoxin-1 |
title_full |
Autonomous Non Antioxidant Roles for Fasciola hepatica Secreted Thioredoxin-1 and Peroxiredoxin-1 |
title_fullStr |
Autonomous Non Antioxidant Roles for Fasciola hepatica Secreted Thioredoxin-1 and Peroxiredoxin-1 |
title_full_unstemmed |
Autonomous Non Antioxidant Roles for Fasciola hepatica Secreted Thioredoxin-1 and Peroxiredoxin-1 |
title_sort |
autonomous non antioxidant roles for fasciola hepatica secreted thioredoxin-1 and peroxiredoxin-1 |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cellular and Infection Microbiology |
issn |
2235-2988 |
publishDate |
2021-05-01 |
description |
Trematode parasites of the genus Fasciola are the cause of liver fluke disease (fasciolosis) in humans and their livestock. Infection of the host involves invasion through the intestinal wall followed by migration in the liver that results in extensive damage, before the parasite settles as a mature egg-laying adult in the bile ducts. Genomic and transcriptomic studies revealed that increased metabolic stress during the rapid growth and development of F. hepatica is balanced with the up-regulation of the thiol-independent antioxidant system. In this cascade system thioredoxin/glutathione reductase (TGR) reduces thioredoxin (Trx), which then reduces and activates peroxiredoxin (Prx), whose major function is to protect cells against the damaging hydrogen peroxide free radicals. F. hepatica expresses a single TGR, three Trx and three Prx genes; however, the transcriptional expression of Trx1 and Prx1 far out-weighs (>50-fold) other members of their family, and both are major components of the parasite secretome. While Prx1 possesses a leader signal peptide that directs its secretion through the classical pathway and explains why this enzyme is found freely soluble in the secretome, Trx1 lacks a leader peptide and is secreted via an alternative pathway that packages the majority of this enzyme into extracellular vesicles (EVs). Here we propose that F. hepatica Prx1 and Trx1 do not function as part of the parasite’s stress-inducible thiol-dependant cascade, but play autonomous roles in defence against the general anti-pathogen oxidative burst by innate immune cells, in the modulation of host immune responses and regulation of inflammation. |
topic |
Fasciola helminth antioxidants thioredoxin thioredoxin peroxidase peroxiredoxin |
url |
https://www.frontiersin.org/articles/10.3389/fcimb.2021.667272/full |
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