{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T00:56:08Z","timestamp":1775177768405,"version":"3.50.1"},"reference-count":115,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T00:00:00Z","timestamp":1620172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001602","name":"Science Foundation Ireland","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>Trematode parasites of the genus <jats:italic>Fasciola<\/jats:italic> 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 <jats:italic>F.\u00a0hepatica<\/jats:italic> 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. <jats:italic>F. hepatica<\/jats:italic> expresses a single TGR, three Trx and three Prx genes; however, the transcriptional expression of Trx1 and Prx1 far out-weighs (&amp;gt;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 <jats:italic>via<\/jats:italic> an alternative pathway that packages the majority of this enzyme into extracellular vesicles (EVs). Here we propose that <jats:italic>F. hepatica<\/jats:italic> Prx1 and Trx1 do not function as part of the parasite\u2019s 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.<\/jats:p>","DOI":"10.3389\/fcimb.2021.667272","type":"journal-article","created":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T05:15:52Z","timestamp":1620191752000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Autonomous Non Antioxidant Roles for Fasciola hepatica Secreted Thioredoxin-1 and Peroxiredoxin-1"],"prefix":"10.3389","volume":"11","author":[{"given":"Amber","family":"Dorey","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krystyna","family":"Cwiklinski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Rooney","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolina","family":"De Marco Verissimo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jes\u00fas","family":"L\u00f3pez Corrales","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heather","family":"Jewhurst","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Fazekas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nichola Eliza Davies","family":"Calvani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siobh\u00e1n","family":"Hamon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siobh\u00e1n","family":"Gaughan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John P.","family":"Dalton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Lalor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,5,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/S0034-5288(18)32535-9","article-title":"Responses of Fluke Infected and Fluke-Free Cattle to Experimental Reinfection With Salmonella Dublin","volume":"31","author":"Aitken","year":"1981","journal-title":"Res. Vet. Sci."},{"key":"B2","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1096\/fj.201500093R","article-title":"The Immune Modulatory Peptide FhHDM-1 Secreted by the Helminth Fasciola Hepatica Prevents NLRP3 Inflammasome Activation by Inhibiting Endolysosomal Acidification in Macrophages","volume":"31","author":"Alvarado","year":"2017","journal-title":"FASEB J."},{"key":"B3","first-page":"1","article-title":"The Life Cycle of Fasciola Hepatica","volume-title":"Fasciolosis","author":"Andrews","year":"1999"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1491","DOI":"10.1073\/pnas.022630299","article-title":"Antigen-Presenting Dendritic Cells Provide the Reducing Extracellular Microenvironment Required for T Lymphocyte Activation","volume":"99","author":"Angelini","year":"2002","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B5","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/j.molbiopara.2016.03.005","article-title":"Typical 2-Cys Peroxiredoxins in Human Parasites: Several Physiological Roles for a Potential Chemotherapy Target","volume":"206","author":"Angelucci","year":"2016","journal-title":"Mol. Biochem. Parasitol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"28977","DOI":"10.1074\/jbc.M109.020701","article-title":"Inhibition of Schistosoma Mansoni Thioredoxin-Glutathione Reductase by Auranofin: Structural and Kinetic Aspects","volume":"284","author":"Angelucci","year":"2009","journal-title":"J. Biol. Chem."},{"key":"B7","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/0014-4894(77)90128-x","article-title":"Fasciola Hepatica: Development of Excretory and Parenchymal Systems During Migration in the Mouse","volume":"41","author":"Bennett","year":"1977","journal-title":"Exp. Parasitol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/0014-4894(73)90066-0","article-title":"Electron Microscope Studies of Fasciola Hepatica. 13. Fine Structure of Newly Excysted Juvenile","volume":"34","author":"Bennett","year":"1973","journal-title":"Exp. Parasitol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1783","DOI":"10.1084\/jem.189.11.1783","article-title":"Thioredoxin, a Redox Enzyme Released in Infection and Inflammation, is a Unique Chemoattractant for Neutrophils, Monocytes, and T Cells","volume":"189","author":"Bertini","year":"1999","journal-title":"J. Exp. Med."},{"key":"B10","doi-asserted-by":"publisher","first-page":"40310","DOI":"10.1074\/jbc.M503644200","article-title":"Extracellular Human Thioredoxin-1 Inhibits Lipopolysaccharide-Induced interleukin-1beta Expression in Human Monocyte-Derived Macrophages","volume":"280","author":"Billiet","year":"2005","journal-title":"J. Biol. Chem."},{"key":"B11","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1083\/jcb.67.3.835","article-title":"Transfer of Proteins Across Membranes. I. Presence of Proteolytically Processed and Unprocessed Nascent Immunoglobulin Light Chains on Membrane-Bound Ribosomes of Murine Myeloma","volume":"67","author":"Blobel","year":"1975","journal-title":"J. Cell Biol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1111\/j.1365-2958.1991.tb00722.x","article-title":"Selenocysteine: The 21st Amino Acid","volume":"5","author":"B\u00f6ck","year":"1991","journal-title":"Mol. Microbiol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.exppara.2015.08.00","article-title":"Oxidative Stress Associated With Pathological Lesions in the Liver of Rats Experimentally Infected by Fasciola Hepatica","volume":"159","author":"Bottari","year":"2015","journal-title":"Exp. Parasitol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"5372","DOI":"10.1128\/IAI.67.10.5372-5378.1999","article-title":"Fasciola Hepatica Suppresses a Protective Th1 Response Against Bordetella Pertussis","volume":"67","author":"Brady","year":"1999","journal-title":"Infect. Immun."},{"key":"B15","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.pt.2020.09.008","article-title":"Fasciola Species Introgression: Just a Fluke or Something More","volume":"37","author":"Calvani","year":"2021","journal-title":"Trends Parasitol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"2335","DOI":"10.1007\/s00436-014-3888-7","article-title":"Identification and Expression of Fasciola Gigantica Thioredoxin","volume":"113","author":"Changklungmoa","year":"2014","journal-title":"Parasitol Res."},{"key":"B17","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/0304-4017(82)90039-5","article-title":"Proteolytic Cleavage of Immunoglobulin by Enzymes Released by Fasciola Hepatica","volume":"11","author":"Chapman","year":"1982","journal-title":"Vet. Parasitol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1227","DOI":"10.1016\/0020-7519(95)00039-5","article-title":"Humoral and Cellular Immune Responses to Fasciola Hepatica Experimental Primary and Secondary Infection in Sheep","volume":"25","author":"Chauvin","year":"1995","journal-title":"Int. J. Parasitol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"8082","DOI":"10.3748\/wjg.v20.i25.8082","article-title":"Oxidative Stress as a Crucial Factor in Liver Diseases","volume":"20","author":"Cicho\u017c-Lach","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.1089\/ars.2010.3114","article-title":"Structure, Function, and Mechanism of Thioredoxin Proteins","volume":"13","author":"Collet","year":"2010","journal-title":"Antioxid Redox Signal."},{"key":"B21","first-page":"1","volume-title":"Importance and Potential Impact of Liver Fluke in Cattle and Buffalo. Overcoming Liver Fluke as a Constraint to Ruminant Production in South-East Asia","author":"Copeman","year":"2008"},{"key":"B22","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1016\/j.ijpara.2017.12.001","article-title":"Advances in Fasciola Hepatica Research Using \u2018Omics\u2019 Technologies","volume":"48","author":"Cwiklinski","year":"2018","journal-title":"Int. J. Parasitol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1186\/s13059-015-0632-2","article-title":"The Fasciola Hepatica Genome: Gene Duplication and Polymorphism Reveals Adaptation to the Host Environment and the Capacity for Rapid Evolution","volume":"16","author":"Cwiklinski","year":"2015","journal-title":"Genome Biol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/bs.apar.2019.01.001","article-title":"The Cathepsin-Like Cysteine Peptidases of Trematodes of the Genus Fasciola","volume":"104","author":"Cwiklinski","year":"2019","journal-title":"Adv. Parasitol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1074\/mcp.RA117.000445","article-title":"Infection by the Helminth Parasite Fasciola Hepatica Requires Rapid Regulation of Metabolic, Virulence, and Invasive Factors to Adjust to its Mammalian Host","volume":"17","author":"Cwiklinski","year":"2018","journal-title":"Mol. Cell Proteomics."},{"key":"B26","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1111\/pim.12343","article-title":"A Prospective View of Animal and Human Fasciolosis","volume":"38","author":"Cwiklinski","year":"2016","journal-title":"Parasite Immunol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1186\/s12864-020-07326-y","article-title":"Complementary Transcriptomic and Proteomic Analyses Reveal the Cellular and Molecular Processes That Drive Growth and Development of Fasciola Hepatica in the Host Liver","volume":"22","author":"Cwiklinski","year":"2021","journal-title":"BMC Genomics"},{"key":"B28","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1017\/S0031182016002043","article-title":"Oxidative Stress and Changes in Adenosine Deaminase Activity of Cattle Experimentally Infected by Fasciola Hepatica","volume":"144","author":"Da Silva","year":"2017","journal-title":"Parasitol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"e0007087","DOI":"10.1371\/journal.pntd.0007087","article-title":"Surface Molecules of Extracellular Vesicles Secreted by the Helminth Pathogen Fasciola Hepatica Direct Their Internalisation by Host Cells","volume":"13","author":"de la Torre-Escudero","year":"2019","journal-title":"PloS Negl. Trop. Dis."},{"key":"B30","doi-asserted-by":"publisher","first-page":"e0008510","DOI":"10.1371\/journal.pntd.0008510","article-title":"Fasciola Hepatica Serine Protease Inhibitor Family (Serpins): Purposely Crafted for Regulating Host Proteases","volume":"14","author":"De Marco Verissimo","year":"2020","journal-title":"PloS Negl. Trop. Dis."},{"key":"B31","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1128\/IAI.73.1.166-173.2005","article-title":"Thioredoxin Peroxidase Secreted by Fasciola Hepatica Induces the Alternative Activation of Macrophages","volume":"73","author":"Donnelly","year":"2005","journal-title":"Infect. Immun."},{"key":"B32","doi-asserted-by":"publisher","first-page":"4022","DOI":"10.1096\/fj.08-106278","article-title":"Helminth 2-Cys Peroxiredoxin Drives Th2 Responses Through a Mechanism Involving Alternatively Activated Macrophages","volume":"22","author":"Donnelly","year":"2008","journal-title":"FASEB J."},{"key":"B33","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1128\/IAI.00573-09","article-title":"Major Secretory Antigens of the Helminth Fasciola Hepatica Activate a Suppressive Dendritic Cell Phenotype That Attenuates Th17 Cells But Fails to Activate Th2 Immune Responses","volume":"78","author":"Dowling","year":"2010","journal-title":"Infect. Immun."},{"key":"B34","doi-asserted-by":"publisher","first-page":"4701","DOI":"10.1038\/emboj.2011.398","article-title":"Autophagy-Based Unconventional Secretory Pathway for Extracellular Delivery of IL-1\u03b2","volume":"30","author":"Dupont","year":"2011","journal-title":"EMBO J."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1443","DOI":"10.1002\/j.1460-2075.1984.tb01994.x","article-title":"Conformational and Functional Similarities Between Glutaredoxin and Thioredoxins","volume":"3","author":"Eklund","year":"1984","journal-title":"EMBO J."},{"key":"B36","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.vetpar.2016.10.020","article-title":"Distribution of Foxp3+ T Cells in the Liver and Hepatic Lymph Nodes of Goats and Sheep Experimentally Infected With Fasciola Hepatica","volume":"230","author":"Escamilla","year":"2016","journal-title":"Vet. Parasitol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.vetpar.2009.12.018","article-title":"Quantitation of Cytokine mRNA by Real-Time RT-PCR During a Vaccination Trial in a Rabbit Model of Fascioliasis","volume":"169","author":"Espino","year":"2009","journal-title":"Vet. Parasitol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"e114505","DOI":"10.1371\/journal.pone.0114505","article-title":"Fasciola Hepatica Kunitz Type Molecule Decreases Dendritic Cell Activation and Their Ability to Induce Inflammatory Responses","volume":"9","author":"Falcon","year":"2014","journal-title":"PloS One"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25215075","article-title":"Repurposing Auranofin and Evaluation of a New Gold(I) Compound for the Search of Treatment of Human and Cattle Parasitic Piseases: From Protozoa to Helminth Infections","volume":"25","author":"Feng","year":"2020","journal-title":"Molecules (Basel Switzerland)"},{"key":"B40","doi-asserted-by":"publisher","first-page":"5005","DOI":"10.1128\/IAI.02541-14","article-title":"Fasciola Hepatica Fatty Acid Binding Protein Induces the Alternative Activation of Human Macrophages","volume":"82","author":"Figueroa-Santiago","year":"2014","journal-title":"Infect. Immun."},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.579801","article-title":"Eosinophils Control Liver Damage by Modulating Immune Responses Against Fasciola Hepatica","volume":"11","author":"Frigerio","year":"2020","journal-title":"Front. Immunol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1016\/j.idc.2012.03.008","article-title":"Trematode Infections: Liver and Lung Flukes","volume":"26","author":"Furst","year":"2012","journal-title":"Infect. Dis. Clin. North Am."},{"key":"B43","first-page":"31","article-title":"Development","volume-title":"Fasciolosis","author":"Graczyk","year":"1999"},{"key":"B44","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/j.parint.2011.01.005","article-title":"Hysteresis in Thioredoxin-Glutathione Reductase (TGR) From the Adult Stage of the Liver Fluke Fasciola Hepatica","volume":"60","author":"Guevara-Flores","year":"2011","journal-title":"Parasitol. Int."},{"key":"B45","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.vetimm.2010.08.007","article-title":"A Preliminary Study to Understand the Effect of Fasciola Hepatica Tegument on Na\u00efve Macrophages and Humoral Responses in an Ovine Model","volume":"139","author":"Ha\u00e7ar\u0131z","year":"2011","journal-title":"Vet. Immunol. Immunopathol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"2469","DOI":"10.1111\/j.1742-4658.2009.06985.x","article-title":"Typical 2-Cys Peroxiredoxins\u2013Structures, Mechanisms and Functions","volume":"276","author":"Hall","year":"2009","journal-title":"FEBS J."},{"key":"B47","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/0014-4894(80)90012-0","article-title":"Fasciola Hepatica: Glycocalyx Replacement in the Juvenile as a Possible Mechanism for Protection Against Host Immunity","volume":"50","author":"Hanna","year":"1980","journal-title":"Exp. Parasitol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/0014-4894(80)90017-x","article-title":"Fasciola Hepatica: An Immunofluorescent Study of Antigenic Changes in the Tegument During Development in the Rat and the Sheep","volume":"50","author":"Hanna","year":"1980","journal-title":"Exp. Parasitol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"1285","DOI":"10.1038\/cr.2015.139","article-title":"Gasdermin D is an Executor of Pyroptosis and Required for Interleukin-1\u03b2 Secretion","volume":"25","author":"He","year":"2015","journal-title":"Cell Res."},{"key":"B50","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.molbiopara.2009.04.008","article-title":"Helminth Immunoregulation: The Role of Parasite Secreted Proteins in Modulating Host Immunity","volume":"167","author":"Hewitson","year":"2009","journal-title":"Mol. Biochem. Parasitol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1186\/s13071-018-2952-z","article-title":"Clonal Amplification of Fasciola Hepatica in Galba Truncatula: Within and Between Isolate Variation of Triclabendazole-Susceptible and -Resistant Clones","volume":"11","author":"Hodgkinson","year":"2018","journal-title":"Parasit Vectors."},{"key":"B52","doi-asserted-by":"publisher","first-page":"91","DOI":"10.3164\/jcbn.11-109","article-title":"Novel Roles of Peroxiredoxins in Inflammation, Cancer and Innate Immunity","volume":"50","author":"Ishii","year":"2012","journal-title":"J. Clin. Biochem. Nutr."},{"key":"B53","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1016\/j.cell.2004.05.002","article-title":"Two Enzymes in One; Two Yeast Peroxiredoxins Display Oxidative Stress-Dependent Switching From a Peroxidase to a Molecular Chaperone Function","volume":"117","author":"Jang","year":"2004","journal-title":"Cell."},{"key":"B54","doi-asserted-by":"publisher","first-page":"1128","DOI":"10.1002\/1615-9861","article-title":"Proteomic Analysis of Fasciola Hepatica Excretory-Secretory Products","volume":"1","author":"Jefferies","year":"2001","journal-title":"Proteomics."},{"key":"B55","doi-asserted-by":"publisher","first-page":"1306","DOI":"10.1016\/j.bbagen.2018.03.007","article-title":"Biochemical and Thermodynamic Comparison of the Selenocysteine Containing and non-Containing Thioredoxin Glutathione Reductase of Fasciola Gigantica","volume":"1862","author":"Kalita","year":"2018","journal-title":"Biochim. Biophys. Acta Gen. Subj."},{"key":"B56","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1128\/CMR.00012-09","article-title":"Food-Borne Trematodiases","volume":"22","author":"Keiser","year":"2009","journal-title":"Clin. Microbiol. Rev."},{"key":"B57","doi-asserted-by":"publisher","first-page":"9494","DOI":"10.1016\/S0021-9258(18)92848-6","article-title":"Mimicking the Active Site of Protein Disulfide-Isomerase by Substitution of Proline 34 in Escherichia Coli Thioredoxin","volume":"266","author":"Krause","year":"1991","journal-title":"J. Biol. Chem."},{"key":"B58","doi-asserted-by":"publisher","first-page":"e206","DOI":"10.1371\/journal.pmed.0040206","article-title":"Thioredoxin Glutathione Reductase From Schistosoma Mansoni: An Essential Parasite Enzyme and a Key Drug Target","volume":"4","author":"Kuntz","year":"2007","journal-title":"PloS Med."},{"key":"B59","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/0304-4017(83)90005-5","article-title":"The Shedding of the Outer Glycocalyx of Juvenile Fasciola Hepatica","volume":"12","author":"Lammas","year":"1983","journal-title":"Vet. Parasitol."},{"key":"B60","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.molbiopara.2008.06.009","article-title":"The Fasciola Hepatica Thioredoxin: High Resolution Structure Reveals Two Oxidation States","volume":"161","author":"Line","year":"2008","journal-title":"Mol. Biochem. Parasitol."},{"key":"B61","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1007\/s00436-016-5327-4","article-title":"Proteomic Analysis of Fasciola Hepatica Excretory and Secretory Products (FhESPs) Involved in Interacting With Host PBMCs and Cytokines by Shotgun LC-MS\/MS","volume":"116","author":"Liu","year":"2017","journal-title":"Parasitol Res."},{"key":"B62","doi-asserted-by":"publisher","first-page":"1259","DOI":"10.1161\/01.res.0000022160.64355.62","article-title":"Thioredoxin Promotes ASK1 Ubiquitination and Degradation to Inhibit ASK1-mediated Apoptosis in a Redox Activity-Independent Manner","volume":"90","author":"Liu","year":"2002","journal-title":"Circ. Res."},{"key":"B63","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1645\/GE-3247","article-title":"Purification, Characterization, and Immunolocalization of a Thioredoxin Reductase From Adult Fasciola Hepatica","volume":"90","author":"Maggioli","year":"2004","journal-title":"J. Parasitol"},{"key":"B64","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1016\/j.exppara.2011.09.013","article-title":"A Recombinant Thioredoxin-Glutathione Reductase From Fasciola Hepatica Induces a Protective Response in Rabbits","volume":"129","author":"Maggioli","year":"2011","journal-title":"Exp. Parasitol"},{"key":"B65","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/S0969-2126(01)00154-X","article-title":"Thioredoxin -a Fold for All Reasons","volume":"3","author":"Martin","year":"1995","journal-title":"Structure."},{"key":"B66","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1007\/978-3-030-18616-6_4","article-title":"Fascioliasis","volume":"1154","author":"Mas-Coma","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"B67","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1017\/s0031182097001170.\u00a0","article-title":"Cloning of Peroxiredoxin, a Novel Antioxidant Enzyme, From the Helminth Parasite Fasciola Hepatica","volume":"115","author":"McGonigle","year":"1997","journal-title":"Parasitol."},{"key":"B68","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/s0169-4758(97)01211-8.\u00a0","article-title":"Peroxidoxins: A New Antioxidant Family","volume":"14","author":"McGonigle","year":"1998","journal-title":"Parasitol Today"},{"key":"B69","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.vetpar.2015.01.004","article-title":"Fasciola Hepatica Vaccine: We may Not be There Yet But We\u2019re on the Right Road","volume":"208","author":"Molina-Hern\u00e1ndez","year":"2015","journal-title":"Vet. Parasitol."},{"key":"B70","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1074\/mcp.M600375-MCP200","article-title":"Comparative Proteomics of Excretory-Secretory Proteins Released by the Liver Fluke Fasciola Hepatica in Sheep Host Bile and During In Vitro Culture Ex Host","volume":"6","author":"Morphew","year":"2007","journal-title":"Mol. Cell Proteomics."},{"key":"B71","doi-asserted-by":"publisher","first-page":"e0008626","DOI":"10.1371\/journal.pntd.0008626","article-title":"Fasciola Hepatica Extracellular Vesicles Isolated From Excretory-Secretory Products Using a Gravity Flow Method Modulate Dendritic Cell Phenotype and Activity","volume":"14","author":"Murphy","year":"2020","journal-title":"PloS neglected Trop. Dis."},{"key":"B72","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/j.mib.2018.09.002","article-title":"Fasciola Hepatica, TGF-\u03b2 and Host Mimicry: The Enemy Within","volume":"46","author":"Musah-Eroje","year":"2018","journal-title":"Curr. Opin. Microbiol."},{"key":"B73","unstructured":"Liver Fluke Control in Sheep"},{"key":"B74","doi-asserted-by":"publisher","first-page":"2688","DOI":"10.1073\/pnas.041624998","article-title":"Chronic Elevation of Plasma Thioredoxin: Inhibition of Chemotaxis and Curtailment of Life Expectancy in AIDS","volume":"98","author":"Nakamura","year":"2001","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1038\/srep40615","article-title":"A Mucin-Like Peptide From Fasciola Hepatica Instructs Dendritic Cells With Parasite Specific Th1-polarizing Activity","volume":"7","author":"Noya","year":"2017","journal-title":"Sci. Rep."},{"key":"B76","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1046\/j.1365-3024.2000.00290.x","article-title":"Fasciola Hepatica Infection Downregulates Th1 Responses in Mice","volume":"22","author":"O\u2019Neill","year":"2000","journal-title":"Parasite Immunol."},{"key":"B77","doi-asserted-by":"publisher","first-page":"254","DOI":"10.4161\/bioe.23612","article-title":"Suppressive Effect of Administration of Recombinant Human Thioredoxin on Cutaneous Inflammation Caused by UV","volume":"4","author":"Ono","year":"2013","journal-title":"Bioengineered."},{"key":"B78","first-page":"261","article-title":"Thioredoxin Specifically Cross-Desensitizes Monocytes to MCP-1","volume":"13","author":"Pagliei","year":"2002","journal-title":"Eur. Cytokine Netw."},{"key":"B79","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1001\/jama.1966.03110210065024","article-title":"Structure and Function At the Cellular Level","volume":"198","author":"Palade","year":"1966","journal-title":"JAMA."},{"key":"B80","doi-asserted-by":"publisher","first-page":"7693","DOI":"10.1021\/bi5013222","article-title":"Tuning of Peroxiredoxin Catalysis for Various Physiological Roles","volume":"53","author":"Perkins","year":"2014","journal-title":"Biochem."},{"key":"B81","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1016\/j.vetpar.2006.05.019","article-title":"Serum Antibody Isotype Responses of Fasciola-infected Sheep and Cattle to Excretory and Secretory Products of Fasciola Species","volume":"141","author":"Phiri","year":"2006","journal-title":"Vet. Parasitol."},{"key":"B82","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1046\/j.1365-3024.2000.00300.x","article-title":"Juvenile Fasciola Hepatica are Resistant to Killing In Vitro by Free Radicals Compared With Larvae of Schistosoma Mansoni","volume":"22","author":"Piedrafita","year":"2000","journal-title":"Parasite Immunol."},{"key":"B83","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1111\/j.1365-3024.2011.01305.x","article-title":"Resistance to Liver Fluke Infection in the Natural Sheep Host is Correlated With a Type-1 Cytokine Response","volume":"33","author":"Pleasance","year":"2011","journal-title":"Parasite Immunol."},{"key":"B84","doi-asserted-by":"publisher","first-page":"8781","DOI":"10.1073\/pnas.1805288115","article-title":"Interleukin 4 is Inactivated Via Selective Disulfide-Bond Reduction by Extracellular Thioredoxin","volume":"115","author":"Plugis","year":"2018","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B85","doi-asserted-by":"publisher","first-page":"5455","DOI":"10.1038\/s41598-017-05735-w","article-title":"Recombinant Fasciola Hepatica Fatty Acid Binding Protein Suppresses Toll-Like Receptor Stimulation in Response to Multiple Bacterial Ligands","volume":"7","author":"Ramos-Ben\u00edtez","year":"2017","journal-title":"Sci. Rep."},{"key":"B86","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1089\/ars.2016.6925","article-title":"Redox Signaling Mediated by Thioredoxin and Glutathione Systems in the Central Nervous System","volume":"27","author":"Ren","year":"2017","journal-title":"Antioxid Redox Signal."},{"key":"B87","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1080\/15216540252774748","article-title":"Peroxiredoxin, a Novel Family of Peroxidases","volume":"52","author":"Rhee","year":"2001","journal-title":"IUBMB Life."},{"key":"B88","doi-asserted-by":"publisher","first-page":"4614","DOI":"10.1096\/fj.12-213876","article-title":"A Helminth Cathelicidin-Like Protein Suppresses Antigen Processing and Presentation in Macrophages Via Inhibition of Lysosomal Vatpase","volume":"26","author":"Robinson","year":"2012","journal-title":"FASEB."},{"key":"B89","doi-asserted-by":"publisher","first-page":"2763","DOI":"10.1098\/rstb.2009.0089","article-title":"Zoonotic Helminth Infections With Particular Emphasis on Fasciolosis and Other Trematodiases","volume":"364","author":"Robinson","year":"2009","journal-title":"Philos. Trans. R. Soc Lond. B. Biol. Sci."},{"key":"B90","doi-asserted-by":"publisher","first-page":"1891","DOI":"10.1074\/mcp.M900045-MCP200","article-title":"An Integrated Transcriptomics and Proteomics Analysis of the Secretome of the Helminth Pathogen Fasciola Hepatica: Proteins Associated With Invasion and Infection of the Mammalian Host","volume":"8","author":"Robinson","year":"2009","journal-title":"Mol. Cell Proteomics."},{"key":"B91","doi-asserted-by":"publisher","first-page":"800","DOI":"10.1016\/j.jmb.2007.02.045","article-title":"The Conserved Active Site Proline Determines the Reducing Power of Staphylococcus Aureus Thioredoxin","volume":"368","author":"Roos","year":"2007","journal-title":"J. Mol. Biol."},{"key":"B92","doi-asserted-by":"publisher","first-page":"2782","DOI":"10.1038\/s41598-017-03094-0","article-title":"Immune Signatures of Pathogenesis in the Peritoneal Compartment During Early Infection of Sheep With Fasciola Hepatica","volume":"7","author":"Ruiz-Campillo","year":"2017","journal-title":"Sci. Rep."},{"key":"B93","doi-asserted-by":"publisher","first-page":"LB287","DOI":"10.1096\/fasebj.28.1_supplement.lb287","article-title":"Interaction of Fasciola Hepatica Fatty Acid Binding Protein With TLR-2: A Preliminary Study to Understand the Immunomodulation Mechanisms That Exert F. Hepatica on the Immune System (LB287)","volume":"28","author":"Ruiz-Jim\u00e9nez","year":"2014","journal-title":"FASEB."},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.02182","article-title":"Fasciola Hepatica-Derived Molecules as Regulators of the Host Immune Response","volume":"11","author":"Ryan","year":"2020","journal-title":"Front. Immunol."},{"key":"B95","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1016\/j.str.2012.01.004","article-title":"Moonlighting by Different Stressors: Crystal Structure of the Chaperone Species of a 2-Cys Peroxiredoxin","volume":"20","author":"Saccoccia","year":"2012","journal-title":"Structure."},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01002","article-title":"The Chronic Stages of Bovine Fasciola Hepatica are Dominated by CD4 T-Cell Exhaustion","volume":"8","author":"Sachdev","year":"2017","journal-title":"Front. Immunol."},{"key":"B97","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1006\/expr.2000.4495","article-title":"Fasciola Hepatica: Heterologous Expression and Functional Characterization of a Thioredoxin Peroxidase","volume":"95","author":"Salazar-Calder\u00f3n","year":"2000","journal-title":"Exp. Parasitol."},{"key":"B98","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1007\/s004360000353","article-title":"Heterologous Expression and Functional Characterization of Thioredoxin From Fasciola Hepatica","volume":"87","author":"Salazar-Calder\u00f3n","year":"2001","journal-title":"Parasitol Res."},{"key":"B99","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1016\/j.vetpar.2008.03.012","article-title":"Circulating Oxidative Stress Status in Desert Sheep Naturally Infected With Fasciola Hepatica","volume":"154","author":"Saleh","year":"2008","journal-title":"Vet. Parasitol."},{"key":"B100","doi-asserted-by":"publisher","first-page":"1672","DOI":"10.1073\/pnas.91.5.1672","article-title":"Distinct Effects of Thioredoxin and Antioxidants on the Activation of Transcription Factors NF-Kappa B and AP-1","volume":"91","author":"Schenk","year":"1994","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B101","doi-asserted-by":"publisher","first-page":"3086","DOI":"10.1038\/sj.emboj.7601746","article-title":"Selective Redox Regulation of Cytokine Receptor Signaling by Extracellular Thioredoxin-1","volume":"26","author":"Schwertassek","year":"2007","journal-title":"EMBO J."},{"key":"B102","doi-asserted-by":"publisher","first-page":"5016","DOI":"10.1016\/j.febslet.2006.08.019.\u00a0","article-title":"Biochemical Characterisation of the Recombinant Peroxiredoxin (FhePrx) of the Liver Fluke, Fasciola Hepatica","volume":"580","author":"Sekiya","year":"2006","journal-title":"FEBS Lett."},{"key":"B103","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/s0304-4017(98)00268-4","article-title":"Bovine T Cell Responses to Recombinant Thioredoxin of Fasciola Hepatica","volume":"82","author":"Shoda","year":"1999","journal-title":"Vet. Parasitol."},{"key":"B104","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1002\/eji.200424500","article-title":"Potential Role of Thioredoxin in Immune Responses in Intestinal Lamina Propria T Lymphocytes","volume":"35","author":"Sido","year":"2005","journal-title":"Eur. J. Immunol."},{"key":"B105","doi-asserted-by":"publisher","first-page":"7799","DOI":"10.1074\/jbc.REV119.008907","article-title":"Evolution, Role in Inflammation, and Redox Control of Leaderless Secretory Proteins","volume":"295","author":"Sitia","year":"2020","journal-title":"J. Biol. Chem."},{"key":"B106","doi-asserted-by":"publisher","first-page":"20657","DOI":"10.1038\/s41598-020-77687-7","article-title":"An Atypical and Functionally Diverse Family of Kunitz-type Cysteine\/Serine Proteinase Inhibitors Secreted by the Helminth Parasite Fasciola Hepatica","volume":"10","author":"Smith","year":"2020","journal-title":"Sci. Rep."},{"key":"B107","doi-asserted-by":"publisher","first-page":"27659","DOI":"10.1074\/jbc.M112.381939","article-title":"Phosphatidylinositol 4,5-Bisphosphate (PI(4,5)P2)-Dependent Oligomerization of Fibroblast Growth Factor 2 (FGF2) Triggers the Formation of a Lipidic Membrane Pore Implicated in Unconventional Secretion","volume":"287","author":"Steringer","year":"2012","journal-title":"J. Biol. Chem."},{"key":"B108","doi-asserted-by":"publisher","first-page":"E616","DOI":"10.1073\/pnas.1419682112","article-title":"Mitochondrial Peroxiredoxin Functions as Crucial Chaperone Reservoir in Leishmania Infantum","volume":"112","author":"Teixeira","year":"2015","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B109","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1046\/j.1365-3024.1998.00144.x","article-title":"Protection of Fasciola Hepatica in the Gut Mucosa of Immune Rats is Associated With Infiltrates of Eosinophils, IgG1 and IgG2a Antibodies Around the Parasites","volume":"20","author":"Van Milligen","year":"1998","journal-title":"Parasite Immunol."},{"key":"B110","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1007\/s00436-013-3650-6","article-title":"Cathepsin L1 Mimotopes With Adjuvant Quil A Induces a Th1\/Th2 Immune Response and Confers Significant Protection Against Fasciola Hepatica Infection in Goats","volume":"113","author":"Villa-Mancera","year":"2014","journal-title":"Parasitol Res."},{"key":"B111","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1038\/nature06414","article-title":"TRPC Channel Activation by Extracellular Thioredoxin","volume":"451","author":"Xu","year":"2008","journal-title":"Nature"},{"key":"B112","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1016\/j.jcpa.2012.08.007","article-title":"Early and Lateperitoneal and Hepatic Changes in Goats Immunized With Recombinantcathepsin L1 and Infected With Fasciola Hepatica","volume":"148","author":"Zafra","year":"2013","journal-title":"J. Comp. Pathol."},{"key":"B113","doi-asserted-by":"publisher","first-page":"602","DOI":"10.1016\/j.rvsc.2012.10.026","article-title":"Early Hepatic and Peritoneal Changes and Immune Response in Goats Vaccinated With a Recombinant Glutathione Transferase Sigma Class and Challenged With Fasciola Hepatica","volume":"94","author":"Zafra","year":"2013","journal-title":"Res. Vet. Sci."},{"key":"B114","doi-asserted-by":"publisher","first-page":"8233","DOI":"10.1074\/jbc.M809338200","article-title":"Molecular Mechanisms of Thioredoxin and Glutaredoxin as Hydrogen Donors for Mammalian s Phase Ribonucleotide Reductase","volume":"284","author":"Zahedi Avval","year":"2009","journal-title":"J. Biol. Chem."},{"key":"B115","doi-asserted-by":"publisher","first-page":"e11205","DOI":"10.7554\/eLife.11205","article-title":"Translocation of Interleukin-1\u03b2 Into a Vesicle Intermediate in Autophagy-Mediated Secretion","volume":"4","author":"Zhang","year":"2015","journal-title":"Elife."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2021.667272\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T05:16:05Z","timestamp":1620191765000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2021.667272\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,5]]},"references-count":115,"alternative-id":["10.3389\/fcimb.2021.667272"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2021.667272","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,5]]},"article-number":"667272"}}