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Review Article

Persistent infectious diseases say – IDO. Role of indoleamine-2,3-dioxygenase in disease pathogenesis and implications for therapy

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Pages 360-368 | Received 05 Jul 2012, Accepted 17 Oct 2012, Published online: 23 Nov 2012

References

  • Adams O, Besken K, Oberdörfer C, MacKenzie CR, Rüssing D, Däubener W. (2004a). Inhibition of human herpes simplex virus type 2 by interferon γ and tumor necrosis factor α is mediated by indoleamine 2,3-dioxygenase. Microbes Infect, 6, 806–812
  • Adams O, Besken K, Oberdörfer C, MacKenzie CR, Takikawa O, Däubener W. (2004b). Role of indoleamine-2,3-dioxygenase in α/β and γ interferon-mediated antiviral effects against herpes simplex virus infections. J Virol, 78, 2632–2636
  • Andersson J, Boasso A, Nilsson J, Zhang R, Shire NJ, Lindback S, Shearer GM, Chougnet CA. (2005). The prevalence of regulatory T cells in lymphoid tissue is correlated with viral load in HIV-infected patients. J Immunol, 174, 3143–3147
  • Baban B, Chandler PR, Sharma MD, Pihkala J, Koni PA, Munn DH, Mellor AL. (2009). IDO activates regulatory T cells and blocks their conversion into Th17-like T cells. J Immunol, 183, 2475–2483
  • Ball HJ, Sanchez-Perez A, Weiser S, Austin CJ, Astelbauer F, Miu J, McQuillan JA, Stocker R, Jermiin LS, Hunt NH. (2007). Characterization of an indoleamine 2,3-dioxygenase-like protein found in humans and mice. Gene, 396, 203–213
  • Banerjee T, Duhadaway JB, Gaspari P, Sutanto-Ward E, Munn DH, Mellor AL, Malachowski WP, Prendergast GC, Muller AJ. (2008). A key in vivo antitumor mechanism of action of natural product-based brassinins is inhibition of indoleamine 2,3-dioxygenase. Oncogene, 27, 2851–2857
  • Belladonna ML, Grohmann U, Guidetti P, Volpi C, Bianchi R, Fioretti MC, Schwarcz R, Fallarino F, Puccetti P. (2006). Kynurenine pathway enzymes in dendritic cells initiate tolerogenesis in the absence of functional IDO. J Immunol, 177, 130–137
  • Belladonna ML, Orabona C, Grohmann U, Puccetti P. (2009). TGF-β and kynurenines as the key to infectious tolerance. Trends Mol Med, 15, 41–49
  • Blaser MJ, Kirschner D. (2007). The equilibria that allow bacterial persistence in human hosts. Nature, 449, 843–849
  • Boasso A, Herbeuval JP, Hardy AW, Anderson SA, Dolan MJ, Fuchs D, Shearer GM. (2007). HIV inhibits CD4+ T-cell proliferation by inducing indoleamine 2,3-dioxygenase in plasmacytoid dendritic cells. Blood, 109, 3351–3359
  • Boasso A, Hardy AW, Anderson SA, Dolan MJ, Shearer GM. (2008). HIV-induced type I interferon and tryptophan catabolism drive T cell dysfunction despite phenotypic activation. PLoS ONE, 3, e2961
  • Boasso A, Vaccari M, Fuchs D, Hardy AW, Tsai WP, Tryniszewska E, Shearer GM, Franchini G. (2009). Combined effect of antiretroviral therapy and blockade of IDO in SIV-infected rhesus macaques. J Immunol, 182, 4313–4320
  • Bodaghi B, Goureau O, Zipeto D, Laurent L, Virelizier JL, Michelson S. (1999). Role of IFN-γ-induced indoleamine 2,3 dioxygenase and inducible nitric oxide synthase in the replication of human cytomegalovirus in retinal pigment epithelial cells. J Immunol, 162, 957–964
  • Bourreau E, Ronet C, Darcissac E, Lise MC, Sainte Marie D, Clity E, Tacchini-Cottier F, Couppie P, Launois P. (2009). Intralesional regulatory T-cell suppressive function during human acute and chronic cutaneous leishmaniasis due to Leishmania guyanensis. Infect Immun, 77, 1465–1474
  • Bozza S, Fallarino F, Pitzurra L, Zelante T, Montagnoli C, Bellocchio S, Mosci P, Vacca C, Puccetti P, Romani L. (2005). A crucial role for tryptophan catabolism at the host/Candida albicans interface. J Immunol, 174, 2910–2918
  • Brenchley JM, Paiardini M, Knox KS, Asher AI, Cervasi B, Asher TE, Scheinberg P, Price DA, Hage CA, Kholi LM, Khoruts A, Frank I, Else J, Schacker T, Silvestri G, Douek DC. (2008). Differential Th17 CD4 T-cell depletion in pathogenic and nonpathogenic lentiviral infections. Blood, 112, 2826–2835
  • Byrne GI, Lehmann LK, Kirschbaum JG, Borden EC, Lee CM, Brown RR. (1986a). Induction of tryptophan degradation in vitro and in vivo: a γ-interferon-stimulated activity. J Interferon Res, 6, 389–396
  • Byrne GI, Lehmann LK, Landry GJ. (1986b). Induction of tryptophan catabolism is the mechanism for γ-interferon-mediated inhibition of intracellular Chlamydia psittaci replication in T24 cells. Infect Immun, 53, 347–351
  • Cameron F, Whiteside G, Perry C. (2011). Ipilimumab: first global approval. Drugs, 71, 1093–1104
  • Chen W, Liang X, Peterson AJ, Munn DH, Blazar BR. (2008). The indoleamine 2,3-dioxygenase pathway is essential for human plasmacytoid dendritic cell-induced adaptive T regulatory cell generation. J Immunol, 181, 5396–5404
  • Cheng SC, van de Veerdonk F, Smeekens S, Joosten LA, van der Meer JW, Kullberg BJ, Netea MG. (2010). Candida albicans dampens host defense by downregulating IL-17 production. J Immunol, 185, 2450–2457
  • Curti A, Trabanelli S, Salvestrini V, Baccarani M, Lemoli RM. (2009). The role of indoleamine 2,3-dioxygenase in the induction of immune tolerance: focus on hematology. Blood, 113, 2394–2401
  • De Luca A, Montagnoli C, Zelante T, Bonifazi P, Bozza S, Moretti S, D’Angelo C, Vacca C, Boon L, Bistoni F, Puccetti P, Fallarino F, Romani L. (2007). Functional yet balanced reactivity to Candida albicans requires TRIF, MyD88, and IDO-dependent inhibition of Rorc. J Immunol, 179, 5999–6008
  • Desvignes L, Ernst JD. (2009). Interferon-γ-responsive nonhematopoietic cells regulate the immune response to Mycobacterium tuberculosis. Immunity, 31, 974–985
  • Divanovic S, Sawtell NM, Trompette A, Warning JI, Dias A, Cooper AM, Yap GS, Arditi M, Shimada K, Duhadaway JB, Prendergast GC, Basaraba RJ, Mellor AL, Munn DH, Aliberti J, Karp CL. (2012). Opposing biological functions of tryptophan catabolizing enzymes during intracellular infection. J Infect Dis, 205, 152–161
  • Estes JD, Li Q, Reynolds MR, Wietgrefe S, Duan L, Schacker T, Picker LJ, Watkins DI, Lifson JD, Reilly C, Carlis J, Haase AT. (2006). Premature induction of an immunosuppressive regulatory T cell response during acute simian immunodeficiency virus infection. J Infect Dis, 193, 703–712
  • Fallarino F, Grohmann U, You S, McGrath BC, Cavener DR, Vacca C, Orabona C, Bianchi R, Belladonna ML, Volpi C, Santamaria P, Fioretti MC, Puccetti P. (2006). The combined effects of tryptophan starvation and tryptophan catabolites down-regulate T cell receptor zeta-chain and induce a regulatory phenotype in naive T cells. J Immunol, 176, 6752–6761
  • Favre D, Lederer S, Kanwar B, Ma ZM, Proll S, Kasakow Z, Mold J, Swainson L, Barbour JD, Baskin CR, Palermo R, Pandrea I, Miller CJ, Katze MG, McCune JM. (2009). Critical loss of the balance between Th17 and T regulatory cell populations in pathogenic SIV infection. PLoS Pathog, 5, e1000295
  • Favre D, Mold J, Hunt PW, Kanwar B, Loke P, Seu L, Barbour JD, Lowe MM, Jayawardene A, Aweeka F, Huang Y, Douek DC, Brenchley JM, Martin JN, Hecht FM, Deeks SG, McCune JM. (2010). Tryptophan catabolism by indoleamine 2,3-dioxygenase 1 alters the balance of TH17 to regulatory T cells in HIV disease. Sci Transl Med, 2, 32ra36
  • Frumento G, Rotondo R, Tonetti M, Damonte G, Benatti U, Ferrara GB. (2002). Tryptophan-derived catabolites are responsible for inhibition of T and natural killer cell proliferation induced by indoleamine 2,3-dioxygenase. J Exp Med, 196, 459–468
  • Grohmann U, Bronte V. (2010). Control of immune response by amino acid metabolism. Immunol Rev, 236, 243–264
  • Hayashi T, Rao SP, Takabayashi K, Van Uden JH, Kornbluth RS, Baird SM, Taylor MW, Carson DA, Catanzaro A, Raz E. (2001). Enhancement of innate immunity against Mycobacterium avium infection by immunostimulatory DNA is mediated by indoleamine 2,3-dioxygenase. Infect Immun, 69, 6156–6164
  • Hayashi T, Beck L, Rossetto C, Gong X, Takikawa O, Takabayashi K, Broide DH, Carson DA, Raz E. (2004). Inhibition of experimental asthma by indoleamine 2,3-dioxygenase. J Clin Invest, 114, 270–279
  • Hayashi T, Mo JH, Gong X, Rossetto C, Jang A, Beck L, Elliott GI, Kufareva I, Abagyan R, Broide DH, Lee J, Raz E. (2007). 3-Hydroxyanthranilic acid inhibits PDK1 activation and suppresses experimental asthma by inducing T cell apoptosis. Proc Natl Acad Sci USA, 104, 18619–18624
  • Hogan RJ, Mathews SA, Mukhopadhyay S, Summersgill JT, Timms P. (2004). Chlamydial persistence: beyond the biphasic paradigm. Infect Immun, 72, 1843–1855
  • Hoshi M, Saito K, Hara A, Taguchi A, Ohtaki H, Tanaka R, Fujigaki H, Osawa Y, Takemura M, Matsunami H, Ito H, Seishima M. (2010). The absence of IDO upregulates type I IFN production, resulting in suppression of viral replication in the retrovirus-infected mouse. J Immunol, 185, 3305–3312
  • Hryniewicz A, Boasso A, Edghill-Smith Y, Vaccari M, Fuchs D, Venzon D, Nacsa J, Betts MR, Tsai WP, Heraud JM, Beer B, Blanset D, Chougnet C, Lowy I, Shearer GM, Franchini G. (2006). CTLA-4 blockade decreases TGF-β, IDO, and viral RNA expression in tissues of SIVmac251-infected macaques. Blood, 108, 3834–3842
  • Idro R, Jenkins NE, Newton CR. (2005). Pathogenesis, clinical features, and neurological outcome of cerebral malaria. Lancet Neurol, 4, 827–840
  • Kaye P, Scott P. (2011). Leishmaniasis: complexity at the host-pathogen interface. Nat Rev Microbiol, 9, 604–615
  • Klinman DM. (2004). Immunotherapeutic uses of CpG oligodeoxynucleotides. Nat Rev Immunol, 4, 249–258
  • Knox WE, Mehler AH. (1950). The conversion of tryptophan to kynurenine in liver. I. The coupled tryptophan peroxidase-oxidase system forming formylkynurenine. J Biol Chem, 187, 419–430
  • Knubel CP, Martínez FF, Fretes RE, Díaz Lujan C, Theumer MG, Cervi L, Motrán CC. (2010). Indoleamine 2,3-dioxigenase (IDO) is critical for host resistance against Trypanosoma cruzi. FASEB J, 24, 2689–2701
  • Knubel CP, Martínez FF, Acosta Rodríguez EV, Altamirano A, Rivarola HW, Diaz Luján C, Fretes RE, Cervi L, Motrán CC. (2011). 3-Hydroxy kynurenine treatment controls T. cruzi replication and the inflammatory pathology preventing the clinical symptoms of chronic Chagas disease. PLoS ONE, 6, e26550
  • Larrea E, Riezu-Boj JI, Gil-Guerrero L, Casares N, Aldabe R, Sarobe P, Civeira MP, Heeney JL, Rollier C, Verstrepen B, Wakita T, Borrás-Cuesta F, Lasarte JJ, Prieto J. (2007). Upregulation of indoleamine 2,3-dioxygenase in hepatitis C virus infection. J Virol, 81, 3662–3666
  • Lau DT, Fish PM, Sinha M, Owen DM, Lemon SM, Gale M Jr. (2008). Interferon regulatory factor-3 activation, hepatic interferon-stimulated gene expression, and immune cell infiltration in hepatitis C virus patients. Hepatology, 47, 799–809
  • Leonhardt RM, Lee SJ, Kavathas PB, Cresswell P. (2007). Severe tryptophan starvation blocks onset of conventional persistence and reduces reactivation of Chlamydia trachomatis. Infect Immun, 75, 5105–5117
  • Löb S, Königsrainer A, Rammensee HG, Opelz G, Terness P. (2009). Inhibitors of indoleamine-2,3-dioxygenase for cancer therapy: can we see the wood for the trees? Nat Rev Cancer, 9, 445–452
  • Makala LH, Baban B, Lemos H, El-Awady AR, Chandler PR, Hou DY, Munn DH, Mellor AL. (2011). Leishmania major attenuates host immunity by stimulating local indoleamine 2,3-dioxygenase expression. J Infect Dis, 203, 715–725
  • Mao R, Zhang J, Jiang D, Cai D, Levy JM, Cuconati A, Block TM, Guo JT, Guo H. (2011). Indoleamine 2,3-dioxygenase mediates the antiviral effect of γ interferon against hepatitis B virus in human hepatocyte-derived cells. J Virol, 85, 1048–1057
  • McGaha TL, Huang L, Lemos H, Metz R, Mautino M, Prendergast GC, Mellor AL. (2012). Amino acid catabolism: a pivotal regulator of innate and adaptive immunity. Immunol Rev, 249, 135–157
  • Mellor AL, Munn DH. (2004). IDO expression by dendritic cells: tolerance and tryptophan catabolism. Nat Rev Immunol, 4, 762–774
  • Mellor AL, Baban B, Chandler PR, Manlapat A, Kahler DJ, Munn DH. (2005). Cutting edge: CpG oligonucleotides induce splenic CD19+ dendritic cells to acquire potent indoleamine 2,3-dioxygenase-dependent T cell regulatory functions via IFN Type 1 signaling. J Immunol, 175, 5601–5605
  • Metz R, Duhadaway JB, Kamasani U, Laury-Kleintop L, Muller AJ, Prendergast GC. (2007). Novel tryptophan catabolic enzyme IDO2 is the preferred biochemical target of the antitumor indoleamine 2,3-dioxygenase inhibitory compound D-1-methyl-tryptophan. Cancer Res, 67, 7082–7087
  • Miu J, Ball HJ, Mellor AL, Hunt NH. (2009). Effect of indoleamine dioxygenase-1 deficiency and kynurenine pathway inhibition on murine cerebral malaria. Int J Parasitol, 39, 363–370
  • Moffett JR, Namboodiri MA. (2003). Tryptophan and the immune response. Immunol Cell Biol, 81, 247–265
  • Montagnoli C, Fallarino F, Gaziano R, Bozza S, Bellocchio S, Zelante T, Kurup WP, Pitzurra L, Puccetti P, Romani L. (2006). Immunity and tolerance to Aspergillus involve functionally distinct regulatory T cells and tryptophan catabolism. J Immunol, 176, 1712–1723
  • Muller AJ, DuHadaway JB, Donover PS, Sutanto-Ward E, Prendergast GC. (2005). Inhibition of indoleamine 2,3-dioxygenase, an immunoregulatory target of the cancer suppression gene Bin1, potentiates cancer chemotherapy. Nat Med, 11, 312–319
  • Muller AJ, Sharma MD, Chandler PR, Duhadaway JB, Everhart ME, Johnson BA 3rd, Kahler DJ, Pihkala J, Soler AP, Munn DH, Prendergast GC, Mellor AL. (2008). Chronic inflammation that facilitates tumor progression creates local immune suppression by inducing indoleamine 2,3 dioxygenase. Proc Natl Acad Sci USA, 105, 17073–17078
  • Munn DH, Zhou M, Attwood JT, Bondarev I, Conway SJ, Marshall B, Brown C, Mellor AL. (1998). Prevention of allogeneic fetal rejection by tryptophan catabolism. Science, 281, 1191–1193
  • Munn DH, Shafizadeh E, Attwood JT, Bondarev I, Pashine A, Mellor AL. (1999). Inhibition of T cell proliferation by macrophage tryptophan catabolism. J Exp Med, 189, 1363–1372
  • Munn DH, Sharma MD, Baban B, Harding HP, Zhang Y, Ron D, Mellor AL. (2005). GCN2 kinase in T cells mediates proliferative arrest and anergy induction in response to indoleamine 2,3-dioxygenase. Immunity, 22, 633–642
  • Munn DH, Mellor AL. (2007). Indoleamine 2,3-dioxygenase and tumor-induced tolerance. J Clin Invest, 117, 1147–1154
  • Murray MF, Langan M, MacGregor RR. (2001). Increased plasma tryptophan in HIV-infected patients treated with pharmacologic doses of nicotinamide. Nutrition, 17, 654–656
  • Murray MF. (2003). Tryptophan depletion and HIV infection: a metabolic link to pathogenesis. Lancet Infect Dis, 3, 644–652
  • Nilsson J, Boasso A, Velilla PA, Zhang R, Vaccari M, Franchini G, Shearer GM, Andersson J, Chougnet C. (2006). HIV-1-driven regulatory T-cell accumulation in lymphoid tissues is associated with disease progression in HIV/AIDS. Blood, 108, 3808–3817
  • Pamer EG. (2004). Immune responses to Listeria monocytogenes. Nat Rev Immunol, 4, 812–823
  • Pereira A, Vottero E, Roberge M, Mauk AG, Andersen RJ. (2006). Indoleamine 2,3-dioxygenase inhibitors from the Northeastern Pacific Marine Hydroid Garveia annulata. J Nat Prod, 69, 1496–1499
  • Pfefferkorn ER. (1984). Interferon γ blocks the growth of Toxoplasma gondii in human fibroblasts by inducing the host cells to degrade tryptophan. Proc Natl Acad Sci USA, 81, 908–912
  • Pilotte L, Larrieu P, Stroobant V, Colau D, Dolusic E, Frédérick R, De Plaen E, Uyttenhove C, Wouters J, Masereel B, Van den Eynde BJ. (2012). Reversal of tumoral immune resistance by inhibition of tryptophan 2,3-dioxygenase. Proc Natl Acad Sci USA, 109, 2497–2502
  • Platten M, Ho PP, Youssef S, Fontoura P, Garren H, Hur EM, Gupta R, Lee LY, Kidd BA, Robinson WH, Sobel RA, Selley ML, Steinman L. (2005). Treatment of autoimmune neuroinflammation with a synthetic tryptophan metabolite. Science, 310, 850–855
  • Popov A, Abdullah Z, Wickenhauser C, Saric T, Driesen J, Hanisch FG, Domann E, Raven EL, Dehus O, Hermann C, Eggle D, Debey S, Chakraborty T, Krönke M, Utermöhlen O, Schultze JL. (2006). Indoleamine 2,3-dioxygenase-expressing dendritic cells form suppurative granulomas following Listeria monocytogenes infection. J Clin Invest, 116, 3160–3170
  • Popov A, Driesen J, Abdullah Z, Wickenhauser C, Beyer M, Debey-Pascher S, Saric T, Kummer S, Takikawa O, Domann E, Chakraborty T, Krönke M, Utermöhlen O, Schultze JL. (2008). Infection of myeloid dendritic cells with Listeria monocytogenes leads to the suppression of T cell function by multiple inhibitory mechanisms. J Immunol, 181, 4976–4988
  • Potula R, Poluektova L, Knipe B, Chrastil J, Heilman D, Dou H, Takikawa O, Munn DH, Gendelman HE, Persidsky Y. (2005). Inhibition of indoleamine 2,3-dioxygenase (IDO) enhances elimination of virus-infected macrophages in an animal model of HIV-1 encephalitis. Blood, 106, 2382–2390
  • Puccetti P, Grohmann U. (2007). IDO and regulatory T cells: a role for reverse signalling and non-canonical NF-kappaB activation. Nat Rev Immunol, 7, 817–823
  • Rehermann B. (2009). Hepatitis C virus versus innate and adaptive immune responses: a tale of coevolution and coexistence. J Clin Invest, 119, 1745–1754
  • Röhrig UF, Awad L, Grosdidier A, Larrieu P, Stroobant V, Colau D, Cerundolo V, Simpson AJ, Vogel P, Van den Eynde BJ, Zoete V, Michielin O. (2010). Rational design of indoleamine 2,3-dioxygenase inhibitors. J Med Chem, 53, 1172–1189
  • Rollier CS, Paranhos-Baccala G, Verschoor EJ, Verstrepen BE, Drexhage JA, Fagrouch Z, Berland JL, Komurian-Pradel F, Duverger B, Himoudi N, Staib C, Meyr M, Whelan M, Whelan JA, Adams VC, Adams VA, Larrea E, Riezu JI, Lasarte JJ, Lasarte JJ, Bartosch B, Cosset FL, Spaan WJ, Diepolder HM, Pape GR, Sutter G, Inchauspe G, Heeney JL. (2007). Vaccine-induced early control of hepatitis C virus infection in chimpanzees fails to impact on hepatic PD-1 and chronicity. Hepatology, 45, 602–613
  • Romani L. (2004). Immunity to fungal infections. Nat Rev Immunol, 4, 1–23
  • Romani L, Fallarino F, De Luca A, Montagnoli C, D’Angelo C, Zelante T, Vacca C, Bistoni F, Fioretti MC, Grohmann U, Segal BH, Puccetti P. (2008). Defective tryptophan catabolism underlies inflammation in mouse chronic granulomatous disease. Nature, 451, 211–215
  • Rouse BT, Sehrawat S. (2010). Immunity and immunopathology to viruses: what decides the outcome? Nat Rev Immunol, 10, 514–526
  • Russell DG. (2007). Who puts the tubercle in tuberculosis? Nat Rev Microbiol, 5, 39–47
  • Sanni LA, Thomas SR, Tattam BN, Moore DE, Chaudhri G, Stocker R, Hunt NH. (1998). Dramatic changes in oxidative tryptophan metabolism along the kynurenine pathway in experimental cerebral and noncerebral malaria. Am J Pathol, 152, 611–619
  • Sarasin-Filipowicz M, Oakeley EJ, Duong FH, Christen V, Terracciano L, Filipowicz W, Heim MH. (2008). Interferon signaling and treatment outcome in chronic hepatitis C. Proc Natl Acad Sci USA, 105, 7034–7039
  • Sarsero JP, Merino E, Yanofsky C. (2000). A Bacillus subtilis operon containing genes of unknown function senses tRNATrp charging and regulates expression of the genes of tryptophan biosynthesis. Proc Natl Acad Sci USA, 97, 2656–2661
  • Seymour RL, Ganapathy V, Mellor AL, Munn DH. (2006). A high-affinity, tryptophan-selective amino acid transport system in human macrophages. J Leukoc Biol, 80, 1320–1327
  • Sharma MD, Hou DY, Liu Y, Koni PA, Metz R, Chandler P, Mellor AL, He Y, Munn DH. (2009). Indoleamine 2,3-dioxygenase controls conversion of Foxp3+ Tregs to TH17-like cells in tumor-draining lymph nodes. Blood, 113, 6102–6111
  • Silva NM, Rodrigues CV, Santoro MM, Reis LF, Alvarez-Leite JI, Gazzinelli RT. (2002). Expression of indoleamine 2,3-dioxygenase, tryptophan degradation, and kynurenine formation during in vivo infection with Toxoplasma gondii: induction by endogenous γ interferon and requirement of interferon regulatory factor 1. Infect Immun, 70, 859–868
  • Sørensen RB, Hadrup SR, Svane IM, Hjortsø MC, Thor Straten P, Andersen MH. (2011). Indoleamine 2,3-dioxygenase specific, cytotoxic T cells as immune regulators. Blood, 117, 2200–2210
  • Southwick FS, Purich DL. (1996). Intracellular pathogenesis of listeriosis. N Engl J Med, 334, 770–776
  • Takahashi K, Asabe S, Wieland S, Garaigorta U, Gastaminza P, Isogawa M, Chisari FV. (2010). Plasmacytoid dendritic cells sense hepatitis C virus-infected cells, produce interferon, and inhibit infection. Proc Natl Acad Sci USA, 107, 7431–7436
  • Takikawa O, Kuroiwa T, Yamazaki F, Kido R. (1988). Mechanism of interferon-γ action. Characterization of indoleamine 2,3-dioxygenase in cultured human cells induced by interferon-γ and evaluation of the enzyme-mediated tryptophan degradation in its anticellular activity. J Biol Chem, 263, 2041–2048
  • Terness P, Bauer TM, Röse L, Dufter C, Watzlik A, Simon H, Opelz G. (2002). Inhibition of allogeneic T cell proliferation by indoleamine 2,3-dioxygenase-expressing dendritic cells: mediation of suppression by tryptophan metabolites. J Exp Med, 196, 447–457
  • Tetsutani K, To H, Torii M, Hisaeda H, Himeno K. (2007). Malaria parasite induces tryptophan-related immune suppression in mice. Parasitology, 134, 923–930
  • Thomas SR, Salahifar H, Mashima R, Hunt NH, Richardson DR, Stocker R. (2001). Antioxidants inhibit indoleamine 2,3-dioxygenase in IFN-γ-activated human macrophages: posttranslational regulation by pyrrolidine dithiocarbamate. J Immunol, 166, 6332–6340
  • Thomas SR, Terentis AC, Cai H, Takikawa O, Levina A, Lay PA, Freewan M, Stocker R. (2007). Post-translational regulation of human indoleamine 2,3-dioxygenase activity by nitric oxide. J Biol Chem, 282, 23778–23787
  • Tsai WL, Chung RT. (2010). Viral hepatocarcinogenesis. Oncogene, 29, 2309–2324
  • Vaccari M, Boasso A, Fenizia C, Fuchs D, Hryniewicz A, Morgan T, Weiss D, Doster MN, Heraud JM, Shearer GM, Franchini G. (2012). Fatal pancreatitis in simian immunodeficiency virus SIV(mac251)-infected macaques treated with 2′,3′-dideoxyinosine and stavudine following cytotoxic-T-lymphocyte-associated antigen 4 and indoleamine 2,3-dioxygenase blockade. J Virol, 86, 108–113
  • Weaver CT, Hatton RD. (2009). Interplay between the TH17 and TReg cell lineages: a (co-)evolutionary perspective. Nat Rev Immunol, 9, 883–889
  • Werner-Felmayer G, Werner ER, Fuchs D, Hausen A, Reibnegger G, Wachter H. (1989). Characteristics of interferon induced tryptophan metabolism in human cells in vitro. Biochim Biophys Acta, 1012, 140–147
  • Williams R. (2006). Global challenges in liver disease. Hepatology, 44, 521–526
  • Wingender G, Garbi N, Schumak B, Jüngerkes F, Endl E, von Bubnoff D, Steitz J, Striegler J, Moldenhauer G, Tüting T, Heit A, Huster KM, Takikawa O, Akira S, Busch DH, Wagner H, Hämmerling GJ, Knolle PA, Limmer A. (2006). Systemic application of CpG-rich DNA suppresses adaptive T cell immunity via induction of IDO. Eur J Immunol, 36, 12–20
  • Xie G, Forst C, Bonner C, Jensen RA. (2002). Significance of two distinct types of tryptophan synthase β chain in Bacteria, Archaea and higher plants. Genome Biol, 3, RESEARCH0004
  • Yan Y, Zhang GX, Gran B, Fallarino F, Yu S, Li H, Cullimore ML, Rostami A, Xu H. (2010). IDO upregulates regulatory T cells via tryptophan catabolite and suppresses encephalitogenic T cell responses in experimental autoimmune encephalomyelitis. J Immunol, 185, 5953–5961
  • Yeung AW, Wu W, Freewan M, Stocker R, King NJ, Thomas SR. (2012). Flavivirus infection induces indoleamine 2,3-dioxygenase in human monocyte-derived macrophages via tumor necrosis factor and NF-κB. J Leukoc Biol, 91, 657–666

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