{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T11:46:06Z","timestamp":1790682366125,"version":"4.1.0"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2015,5,15]],"date-time":"2015-05-15T00:00:00Z","timestamp":1431648000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000106","name":"Saskatchewan Health Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000106","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,5,15]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Dendritic cells (DCs) play an important role in the induction of the primary immune response to infection. DCs may express the tryptophan-catabolizing enzyme indolamine2,3-dioxygenase (IDO), which is an inducer of immune tolerance. Because there is evidence that chronic hepatitis C virus (HCV) infection leads to functional impairment of certain DC populations, we analysed IDO expression in DCs and monocytes from chronically infected and recovered HCV patients. The IDO1 and -2 expression was increased significantly in the monocytes of chronic HCV patients but, interestingly, not in those from recovered patients. The myeloid DCs from chronically infected HCV patients also showed enhanced IDO1 expression, while no change in either IDO1 or -2 was found for plasmacytoid DCs. Up-regulation of IDO1 gene expression was confirmed by the presence of enhanced kynurenine\/tryptophan ratios in the plasma from chronic HCV patients. Increased IDO1 and -2 expression was also observed in monocytes from healthy donors infected with an adapted mutant of the HCV JFH-1 strain ex vivo, confirming a direct effect of HCV infection. These changes in IDO expression could be prevented by treatment with the IDO inhibitor 1-methyl tryptophan (1-mT). Furthermore, maturation of monocyte-derived DCs from chronically infected HCV patients, as well as well as monocyte-derived DCs infected ex vivo with HCV, was impaired, but this was reversed by 1-mT treatment. This suggests that IDO inhibitors may be used to treat chronic HCV patients in vivo, in conjunction with current therapies, or to activate DCs from patients ex vivo, such that they can be administered back as a DC-based therapeutic vaccine.<\/jats:p>","DOI":"10.1111\/cei.12586","type":"journal-article","created":{"date-parts":[[2015,1,20]],"date-time":"2015-01-20T14:08:44Z","timestamp":1421762924000},"page":"484-498","source":"Crossref","is-referenced-by-count":27,"title":["Indolamine 2,3-dioxygenase expression by monocytes and dendritic cell populations in hepatitis C patients"],"prefix":"10.1093","volume":"180","author":[{"given":"S","family":"Schulz","sequence":"first","affiliation":[{"name":"VIDO-InterVac, University of Saskatchewan, Saskatoon, Saskatchewan, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Landi","sequence":"additional","affiliation":[{"name":"Li Ka Shing Institute of Virology, Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Garg","sequence":"additional","affiliation":[{"name":"VIDO-InterVac, University of Saskatchewan, Saskatoon, Saskatchewan, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J A","family":"Wilson","sequence":"additional","affiliation":[{"name":"Microbiology and Immunology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"van Drunen Littel-van den Hurk","sequence":"additional","affiliation":[{"name":"VIDO-InterVac, University of Saskatchewan, Saskatoon, Saskatchewan, Canada"},{"name":"Microbiology and Immunology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,5,15]]},"reference":[{"key":"2021122010143304300_cei12586-bib-0001","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/j.cld.2006.08.003","article-title":"The changing epidemiology and natural history of hepatitis C virus infection","volume":"10","author":"Bialek","year":"2006","journal-title":"Clin Liver Dis"},{"key":"2021122010143304300_cei12586-bib-0002","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1016\/S1473-3099(05)70216-4","article-title":"Global epidemiology of hepatitis C virus infection","volume":"5","author":"Shepard","year":"2005","journal-title":"Lancet Infect Dis"},{"key":"2021122010143304300_cei12586-bib-0003","first-page":"S21","article-title":"Understanding hepatitis C","volume":"10","author":"McHutchison","year":"2004","journal-title":"Am J Manag Care"},{"key":"2021122010143304300_cei12586-bib-0004","first-page":"5","volume-title":"The Medical Letter for Drugs and Therapeutics","author":"The Medical Letter I","year":"2014"},{"key":"2021122010143304300_cei12586-bib-0005","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1189\/jlb.0408241","article-title":"Modulation of dendritic cell function by persistent viruses","volume":"85","author":"Liu","year":"2009","journal-title":"J Leukoc Biol"},{"key":"2021122010143304300_cei12586-bib-0006","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/j.imbio.2010.11.004","article-title":"Dendritic cells matured by a prostaglandin E2-containing cocktail can produce high levels of IL-12p70 and are more mature and Th1-biased than dendritic cells treated with TNF-alpha or LPS","volume":"216","author":"Landi","year":"2011","journal-title":"Immunobiology"},{"key":"2021122010143304300_cei12586-bib-0007","volume-title":"Dendritic cells: a basic review","author":"Wieder","year":"2003"},{"key":"2021122010143304300_cei12586-bib-0008","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1038\/nri1457","article-title":"IDO expression by dendritic cells: tolerance and tryptophan catabolism","volume":"4","author":"Mellor","year":"2004","journal-title":"Nat Rev Immunol"},{"key":"2021122010143304300_cei12586-bib-0009","doi-asserted-by":"crossref","first-page":"32ra6","DOI":"10.1126\/scitranslmed.3000632","article-title":"Tryptophan catabolism by indoleamine 2,3-dioxygenase 1 alters the balance of TH17 to regulatory T cells in HIV disease","volume":"2","author":"Favre","year":"2010","journal-title":"Sci Transl Med"},{"key":"2021122010143304300_cei12586-bib-0010","doi-asserted-by":"crossref","first-page":"3351","DOI":"10.1182\/blood-2006-07-034785","article-title":"HIV inhibits CD4+ T-cell proliferation by inducing indoleamine 2,3-dioxygenase in plasmacytoid dendritic cells","volume":"109","author":"Boasso","year":"2007","journal-title":"Blood"},{"key":"2021122010143304300_cei12586-bib-0011","doi-asserted-by":"crossref","first-page":"3662","DOI":"10.1128\/JVI.02248-06","article-title":"Upregulation of indoleamine 2,3-dioxygenase in hepatitis C virus infection","volume":"81","author":"Larrea","year":"2007","journal-title":"J Virol"},{"key":"2021122010143304300_cei12586-bib-0012","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1007\/s00535-012-0667-z","article-title":"Association of enhanced activity of indoleamine 2,3-dioxygenase in dendritic cells with the induction of regulatory T cells in chronic hepatitis C infection","volume":"48","author":"Higashitani","year":"2013","journal-title":"J Gastroenterol"},{"key":"2021122010143304300_cei12586-bib-0013","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1111\/j.1365-2893.2005.00706.x","article-title":"Low serum tryptophan levels, reduced macrophage IDO activity and high frequency of psychopathology in HCV patients","volume":"13","author":"Cozzi","year":"2006","journal-title":"J Viral Hepat"},{"key":"2021122010143304300_cei12586-bib-0014","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/s00262-008-0513-6","article-title":"IDO1 and IDO2 are expressed in human tumors: levo- but not dextro-1-methyl tryptophan inhibits tryptophan catabolism","volume":"58","author":"Lob","year":"2009","journal-title":"Cancer Immunol Immunother"},{"key":"2021122010143304300_cei12586-bib-0015","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1007\/s00262-012-1265-x","article-title":"Effects of 1-methyltryptophan stereoisomers on IDO2 enzyme activity and IDO2-mediated arrest of human T cell proliferation","volume":"61","author":"Qian","year":"2012","journal-title":"Cancer Immunol Immunother"},{"key":"2021122010143304300_cei12586-bib-0016","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1189\/jlb.0906561","article-title":"High transfection efficiency, gene expression, and viability of monocyte-derived human dendritic cells after nonviral gene transfer","volume":"82","author":"Landi","year":"2007","journal-title":"J Leukoc Biol"},{"key":"2021122010143304300_cei12586-bib-0017","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/1743-422X-7-40","article-title":"Thermal stability and inactivation of hepatitis C virus grown in cell culture","volume":"7","author":"Song","year":"2010","journal-title":"Virol J"},{"key":"2021122010143304300_cei12586-bib-0018","doi-asserted-by":"crossref","first-page":"4370","DOI":"10.1073\/pnas.0800422105","article-title":"Advantages of a single-cycle production assay to study cell culture-adaptive mutations of hepatitis C virus","volume":"105","author":"Russell","year":"2008","journal-title":"Proc Natl Acad Sci USA"},{"key":"2021122010143304300_cei12586-bib-0019","doi-asserted-by":"crossref","first-page":"8189","DOI":"10.1128\/JVI.76.16.8189-8199.2002","article-title":"Alpha interferon inhibits hepatitis C virus replication in primary human hepatocytes infected in vitro","volume":"76","author":"Castet","year":"2002","journal-title":"J Virol"},{"key":"2021122010143304300_cei12586-bib-0020","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1099\/vir.0.83517-0","article-title":"Altered chemotactic response of myeloid and plasmacytoid dendritic cells from patients with chronic hepatitis C: role of alpha interferon","volume":"89","author":"Cicinnati","year":"2008","journal-title":"J Gen Virol"},{"key":"2021122010143304300_cei12586-bib-0021","doi-asserted-by":"crossref","first-page":"7431","DOI":"10.1073\/pnas.1002301107","article-title":"Plasmacytoid dendritic cells sense hepatitis C virus-infected cells, produce interferon, and inhibit infection","volume":"107","author":"Takahashi","year":"2010","journal-title":"Proc Natl Acad Sci USA"},{"key":"2021122010143304300_cei12586-bib-0022","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1111\/j.1365-2893.2011.01453.x","article-title":"The affect of chronic hepatitis C infection on dendritic cell function: a summary of the experimental evidence","volume":"18","author":"Ryan","year":"2011","journal-title":"J Viral Hepat"},{"key":"2021122010143304300_cei12586-bib-0023","doi-asserted-by":"crossref","first-page":"610","DOI":"10.4161\/viru.21823","article-title":"Dendritic cells, regulatory T cells and the pathogenesis of chronic hepatitis C","volume":"3","author":"Losikoff","year":"2012","journal-title":"Virulence"},{"key":"2021122010143304300_cei12586-bib-0024","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1016\/S0168-8278(02)00062-4","article-title":"Phenotypic analysis of circulating and intrahepatic dendritic cell subsets in patients with chronic liver diseases","volume":"36","author":"Kunitani","year":"2002","journal-title":"J Hepatol"},{"key":"2021122010143304300_cei12586-bib-0025","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1002\/hep.21996","article-title":"Cell culture-produced hepatitis C virus impairs plasmacytoid dendritic cell function","volume":"47","author":"Shiina","year":"2008","journal-title":"Hepatology"},{"key":"2021122010143304300_cei12586-bib-0026","doi-asserted-by":"crossref","first-page":"2423","DOI":"10.1084\/jem.20070814","article-title":"Plasmacytoid dendritic cells initiate a complex chemokine and cytokine network and are a viable drug target in chronic HCV patients","volume":"204","author":"Decalf","year":"2007","journal-title":"J Exp Med"},{"key":"2021122010143304300_cei12586-bib-0027","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1086\/656777","article-title":"Circulating plasmacytoid dendritic cells in acutely infected patients with hepatitis C virus genotype 4 are normal in number and phenotype","volume":"202","author":"Mansour","year":"2010","journal-title":"J Infect Dis"},{"key":"2021122010143304300_cei12586-bib-0028","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1016\/j.jhep.2008.09.002","article-title":"Plasmacytoid dendritic cells move down on the list of suspects: in search of the immune pathogenesis of chronic hepatitis C","volume":"49","author":"Albert","year":"2008","journal-title":"J Hepatol"},{"key":"2021122010143304300_cei12586-bib-0029","doi-asserted-by":"crossref","first-page":"6701","DOI":"10.4049\/jimmunol.1003151","article-title":"Identification of IDO-positive and IDO-negative human dendritic cells after activation by various proinflammatory stimuli","volume":"186","author":"Von Bubnoff","year":"2011","journal-title":"J Immunol"},{"key":"2021122010143304300_cei12586-bib-0030","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1097\/IGC.0b013e31822017fb","article-title":"Serum tryptophan and kynurenine concentrations as parameters for indoleamine 2,3-dioxygenase activity in patients with endometrial, ovarian, and vulvar cancer","volume":"21","author":"de Jong","year":"2011","journal-title":"Int J Gynecol Cancer"},{"key":"2021122010143304300_cei12586-bib-0031","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.lungcan.2009.05.001","article-title":"Increased serum kynurenine\/tryptophan ratio correlates with disease progression in lung cancer","volume":"67","author":"Suzuki","year":"2010","journal-title":"Lung Cancer"},{"key":"2021122010143304300_cei12586-bib-0032","doi-asserted-by":"crossref","first-page":"2152","DOI":"10.1182\/blood-2007-10-116111","article-title":"Levo- but not dextro-1-methyl tryptophan abrogates the IDO activity of human dendritic cells","volume":"111","author":"Lob","year":"2008","journal-title":"Blood"},{"key":"2021122010143304300_cei12586-bib-0033","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1007\/s10616-007-9081-4","article-title":"Transcriptional regulation of indoleamine 2,3-dioxygenase (IDO) by tryptophan and its analogue: down-regulation of the indoleamine 2,3-dioxygenase (IDO) transcription by tryptophan and its analogue","volume":"54","author":"Okamoto","year":"2007","journal-title":"Cytotechnology"},{"key":"2021122010143304300_cei12586-bib-0034","doi-asserted-by":"crossref","first-page":"2061","DOI":"10.4049\/jimmunol.177.4.2061","article-title":"1-Methyl-tryptophan can interfere with TLR signaling in dendritic cells independently of IDO activity","volume":"177","author":"Agaugue","year":"2006","journal-title":"J Immunol"},{"key":"2021122010143304300_cei12586-bib-0035","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.ygyno.2009.07.015","article-title":"Role of the immunosuppressive enzyme indoleamine 2,3-dioxygenase in the progression of ovarian carcinoma","volume":"115","author":"Inaba","year":"2009","journal-title":"Gynecol Oncol"},{"key":"2021122010143304300_cei12586-bib-0036","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1186\/1743-422X-8-346","article-title":"Human cell types important for hepatitis C virus replication in vivo and in vitro: old assertions and current evidence","volume":"8","author":"Revie","year":"2011","journal-title":"Virol J"},{"key":"2021122010143304300_cei12586-bib-0037","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1136\/gutjnl-2011-300620","article-title":"T cell responses in hepatitis C: the good, the bad and the unconventional","volume":"61","author":"Klenerman","year":"2012","journal-title":"Gut"},{"key":"2021122010143304300_cei12586-bib-0038","doi-asserted-by":"crossref","first-page":"2777","DOI":"10.3748\/wjg.v20.i11.2777","article-title":"Role of macrophages and monocytes in hepatitis C virus infections","volume":"20","author":"Revie","year":"2014","journal-title":"World J Gastroenterol"},{"key":"2021122010143304300_cei12586-bib-0039","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1002\/jmv.21388","article-title":"Infection of B cells with hepatitis C virus for the development of lymphoproliferative disorders in patients with chronic hepatitis C","volume":"81","author":"Inokuchi","year":"2009","journal-title":"J Med Virol"},{"key":"2021122010143304300_cei12586-bib-0040","doi-asserted-by":"crossref","first-page":"5693","DOI":"10.1128\/JVI.02671-08","article-title":"Differential effects of hepatitis C virus JFH1 on human myeloid and plasmacytoid dendritic cells","volume":"83","author":"Liang","year":"2009","journal-title":"J Virol"},{"key":"2021122010143304300_cei12586-bib-0041","doi-asserted-by":"crossref","first-page":"5867","DOI":"10.1128\/JVI.78.11.5867-5874.2004","article-title":"Hepatitis C virus persistence after spontaneous or treatment-induced resolution of hepatitis C","volume":"78","author":"Pham","year":"2004","journal-title":"J Virol"},{"key":"2021122010143304300_cei12586-bib-0042","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.1002\/hep.22550","article-title":"Cell culture-produced hepatitis C virus does not infect peripheral blood mononuclear cells","volume":"48","author":"Marukian","year":"2008","journal-title":"Hepatology"},{"key":"2021122010143304300_cei12586-bib-0043","doi-asserted-by":"crossref","first-page":"7525","DOI":"10.4049\/jimmunol.180.11.7525","article-title":"Glycoprotein-dependent and TLR2-independent innate immune recognition of herpes simplex virus-1 by dendritic cells","volume":"180","author":"Reske","year":"2008","journal-title":"J Immunol"},{"key":"2021122010143304300_cei12586-bib-0044","doi-asserted-by":"crossref","first-page":"3171","DOI":"10.1182\/blood.V97.10.3171","article-title":"Impaired dendritic cell maturation in patients with chronic, but not resolved, hepatitis C virus infection","volume":"97","author":"Auffermann-Gretzinger","year":"2001","journal-title":"Blood"},{"key":"2021122010143304300_cei12586-bib-0045","doi-asserted-by":"crossref","first-page":"3320","DOI":"10.1128\/JVI.02547-07","article-title":"Hepatitis C virus inhibits cell surface expression of HLA-DR, prevents dendritic cell maturation, and induces interleukin-10 production","volume":"82","author":"Saito","year":"2008","journal-title":"J Virol"},{"key":"2021122010143304300_cei12586-bib-0046","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1111\/j.1365-2249.2007.03367.x","article-title":"Monocyte-derived dendritic cell function in chronoc hepatitis C is impaired at physiological numbers of dendritic cells","volume":"148","author":"MacDonald","year":"2007","journal-title":"Clin Exp Immunol"},{"key":"2021122010143304300_cei12586-bib-0047","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1084\/jem.20020052","article-title":"Inhibition of allogeneic T cell proliferation by indoleamine 2,3-dioxygenase-expressing dendritic cells: mediation of suppression by tryptophan metabolites","volume":"196","author":"Terness","year":"2002","journal-title":"J Exp Med"},{"key":"2021122010143304300_cei12586-bib-0048","doi-asserted-by":"crossref","first-page":"2375","DOI":"10.1182\/blood-2005-03-0979","article-title":"A two-step induction of indoleamine 2,3 dioxygenase (IDO) activity during dendritic-cell maturation","volume":"106","author":"Braun","year":"2005","journal-title":"Blood"},{"key":"2021122010143304300_cei12586-bib-0049","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1002\/eji.201141765","article-title":"Ambivalent effects of dendritic cells displaying prostaglandin E2-induced indoleamine 2,3-dioxygenase","volume":"42","author":"Lanzinger","year":"2012","journal-title":"Eur J Immunol"},{"key":"2021122010143304300_cei12586-bib-0050","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1189\/jlb.0905519","article-title":"Prostaglandin E2 is a key factor for monocyte-derived dendritic cell maturation: enhanced T cell stimulatory capacity despite IDO","volume":"82","author":"Krause","year":"2007","journal-title":"J Leukoc Biol"},{"key":"2021122010143304300_cei12586-bib-0051","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1182\/blood-2005-08-3507","article-title":"CD25 and indoleamine 2,3-dioxygenase are up-regulated by prostaglandin E2 and expressed by tumor-associated dendritic cells in vivo: additional mechanisms of T-cell inhibition","volume":"108","author":"von Bergwelt-Baildon","year":"2006","journal-title":"Blood"},{"key":"2021122010143304300_cei12586-bib-0052","doi-asserted-by":"crossref","first-page":"9725","DOI":"10.1128\/JVI.79.15.9725-9734.2005","article-title":"Hepatitis C virus stimulates the expression of cyclooxygenase-2 via oxidative stress: role of prostaglandin E2 in RNA replication","volume":"79","author":"Waris","year":"2005","journal-title":"J Virol"}],"container-title":["Clinical and Experimental Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcei.12586","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/180\/3\/484\/41791401\/cei12586.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/180\/3\/484\/41791401\/cei12586.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,17]],"date-time":"2025-05-17T06:13:34Z","timestamp":1747462414000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cei\/article\/180\/3\/484\/6422190"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,5,15]]},"references-count":52,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2015,5,15]]},"published-print":{"date-parts":[[2015,5,15]]}},"URL":"https:\/\/doi.org\/10.1111\/cei.12586","relation":{},"ISSN":["0009-9104","1365-2249"],"issn-type":[{"value":"0009-9104","type":"print"},{"value":"1365-2249","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2015,6]]},"published":{"date-parts":[[2015,5,15]]}}}