PMID- 25605587 OWN - NLM STAT- MEDLINE DCOM- 20150811 LR - 20190109 IS - 1365-2249 (Electronic) IS - 0009-9104 (Print) IS - 0009-9104 (Linking) VI - 180 IP - 3 DP - 2015 Jun TI - Indolamine 2,3-dioxygenase expression by monocytes and dendritic cell populations in hepatitis C patients. PG - 484-98 LID - 10.1111/cei.12586 [doi] AB - 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. CI - (c) 2015 British Society for Immunology. FAU - Schulz, S AU - Schulz S AD - VIDO-InterVac, University of Saskatchewan, Saskatoon, Saskatchewan, Canada. FAU - Landi, A AU - Landi A AD - Li Ka Shing Institute of Virology, Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada. FAU - Garg, R AU - Garg R AD - VIDO-InterVac, University of Saskatchewan, Saskatoon, Saskatchewan, Canada. FAU - Wilson, J A AU - Wilson JA AD - Microbiology and Immunology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada. FAU - van Drunen Littel-van den Hurk, S AU - van Drunen Littel-van den Hurk S AD - VIDO-InterVac, University of Saskatchewan, Saskatoon, Saskatchewan, Canada. AD - Microbiology and Immunology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada. LA - eng GR - Canadian Institutes of Health Research/Canada PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Clin Exp Immunol JT - Clinical and experimental immunology JID - 0057202 RN - 0 (Chemokines) RN - 0 (Cytokines) RN - 0 (Indoleamine-Pyrrole 2,3,-Dioxygenase) RN - 0 (Inflammation Mediators) RN - 0 (RNA, Messenger) RN - 343-65-7 (Kynurenine) RN - 8DUH1N11BX (Tryptophan) RN - XD0FY1J13B (1-methyltryptophan) SB - IM MH - Adult MH - Aged MH - Case-Control Studies MH - Chemokines/blood MH - Cytokines/blood MH - Dendritic Cells/*immunology/*metabolism MH - Female MH - *Gene Expression MH - Gene Expression Regulation/drug effects MH - Genotype MH - Hepacivirus/genetics/*immunology MH - Hepatitis C/drug therapy/*genetics/*immunology/metabolism/virology MH - Humans MH - Indoleamine-Pyrrole 2,3,-Dioxygenase/*genetics/metabolism MH - Inflammation Mediators/blood MH - Kynurenine/blood MH - Leukocyte Count MH - Male MH - Middle Aged MH - Monocytes/*immunology/*metabolism/virology MH - RNA, Messenger/genetics MH - Tryptophan/analogs & derivatives/blood/pharmacology/therapeutic use MH - Viral Load MH - Virus Replication MH - Young Adult PMC - PMC4449777 OTO - NOTNLM OT - IDO OT - dendritic cell OT - hepatitis C virus OT - monocyte EDAT- 2015/01/22 06:00 MHDA- 2015/08/12 06:00 PMCR- 2016/06/01 CRDT- 2015/01/22 06:00 PHST- 2014/07/09 00:00 [received] PHST- 2014/12/31 00:00 [revised] PHST- 2015/01/09 00:00 [accepted] PHST- 2015/01/22 06:00 [entrez] PHST- 2015/01/22 06:00 [pubmed] PHST- 2015/08/12 06:00 [medline] PHST- 2016/06/01 00:00 [pmc-release] AID - 10.1111/cei.12586 [doi] PST - ppublish SO - Clin Exp Immunol. 2015 Jun;180(3):484-98. doi: 10.1111/cei.12586.