1887

Abstract

Influenza infection induces an increase in the level of indoleamine 2,3-dioxygenase (IDO) activity in the lung parenchyma. IDO is the first and rate-limiting step in the kynurenine pathway where tryptophan is reduced to kynurenine and other metabolites. The depletion of tryptophan, and production of associated metabolites, attenuates the immune response to infection. The impact of IDO on the primary immune response to influenza virus infection was determined using the IDO inhibitor 1-methyl-,-tryptophan (1MT). C57BL/6 mice treated with 1MT and infected with A/HKx31 influenza virus had increased numbers of activated and functional CD4 T-cells, influenza-specific CD8 T-cells and effector memory cells in the lung. Inhibition of IDO increased the Th1 response in CD4 T-cells as well as enhanced the Th17 response. These studies show that inhibition of IDO engenders a more robust T-cell response to influenza virus, and suggests an approach for enhancing the immune response to influenza vaccination by facilitating increased influenza-specific T-cell response.

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2013-07-01
2020-01-17
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References

  1. Andersson J. , Boasso A. , Nilsson J. , Zhang R. , Shire N. J. , Lindback S. , Shearer G. M. , Chougnet C. A. . ( 2005; ). The prevalence of regulatory T cells in lymphoid tissue is correlated with viral load in HIV-infected patients. . J Immunol 174:, 3143–3147.[PubMed] [CrossRef]
    [Google Scholar]
  2. Baban B. , Chandler P. R. , Sharma M. D. , Pihkala J. , Koni P. A. , Munn D. H. , Mellor A. L. . ( 2009; ). IDO activates regulatory T cells and blocks their conversion into Th17-like T cells. . J Immunol 183:, 2475–2483. [CrossRef] [PubMed]
    [Google Scholar]
  3. Baban B. , Chandler P. R. , Johnson B. A. III , Huang L. , Li M. , Sharpe M. L. , Francisco L. M. , Sharpe A. H. , Blazar B. R. . & other authors ( 2011; ). Physiologic control of IDO competence in splenic dendritic cells. . J Immunol 187:, 2329–2335. [CrossRef] [PubMed]
    [Google Scholar]
  4. Bianchi M. , Bertini R. , Ghezzi P. . ( 1988; ). Induction of indoleamine dioxygenase by interferon in mice: a study with different recombinant interferons and various cytokines. . Biochem Biophys Res Commun 152:, 237–242. [CrossRef] [PubMed]
    [Google Scholar]
  5. Boasso A. , Herbeuval J. P. , Hardy A. W. , Anderson S. A. , Dolan M. J. , Fuchs D. , Shearer G. M. . ( 2007; ). HIV inhibits CD4+ T-cell proliferation by inducing indoleamine 2,3-dioxygenase in plasmacytoid dendritic cells. . Blood 109:, 3351–3359. [CrossRef] [PubMed]
    [Google Scholar]
  6. Bridges C. B. , Katz J. M. , Levandowski R. A. , Cox N. J. . ( 2008; ). Inactivated influenza vaccines. . In Vaccines, pp. 259–290. Edited by Potkin S. A. , Orenstein W. A. , Offit P. A. . . Philadelphia, PA:: Elsevier;.
    [Google Scholar]
  7. Brown J. A. , Dorfman D. M. , Ma F. R. , Sullivan E. L. , Munoz O. , Wood C. R. , Greenfield E. A. , Freeman G. J. . ( 2003; ). Blockade of programmed death-1 ligands on dendritic cells enhances T cell activation and cytokine production. . J Immunol 170:, 1257–1266.[PubMed] [CrossRef]
    [Google Scholar]
  8. Cady S. G. , Sono M. . ( 1991; ). 1-Methyl-dl-tryptophan, beta-(3-benzofuranyl)-dl-alanine (the oxygen analog of tryptophan), and beta-[3-benzo(b)thienyl]-dl-alanine (the sulfur analog of tryptophan) are competitive inhibitors for indoleamine 2,3-dioxygenase. . Arch Biochem Biophys 291:, 326–333. [CrossRef] [PubMed]
    [Google Scholar]
  9. Cella M. , Facchetti F. , Lanzavecchia A. , Colonna M. . ( 2000; ). Plasmacytoid dendritic cells activated by influenza virus and CD40L drive a potent TH1 polarization. . Nat Immunol 1:, 305–310. [CrossRef] [PubMed]
    [Google Scholar]
  10. Crowe S. R. , Turner S. J. , Miller S. C. , Roberts A. D. , Rappolo R. A. , Doherty P. C. , Ely K. H. , Woodland D. L. . ( 2003; ). Differential antigen presentation regulates the changing patterns of CD8+ T cell immunodominance in primary and secondary influenza virus infections. . J Exp Med 198:, 399–410. [CrossRef] [PubMed]
    [Google Scholar]
  11. Crowe S. R. , Miller S. C. , Woodland D. L. . ( 2006; ). Identification of protective and non-protective T cell epitopes in influenza. . Vaccine 24:, 452–456. [CrossRef] [PubMed]
    [Google Scholar]
  12. Culley F. J. . ( 2009; ). Natural killer cells in infection and inflammation of the lung. . Immunology 128:, 151–163. [CrossRef] [PubMed]
    [Google Scholar]
  13. Dai H. , Dai Z. . ( 2008; ). The role of tryptophan catabolism in acquisition and effector function of memory T cells. . Curr Opin Organ Transplant 13:, 31–35. [CrossRef] [PubMed]
    [Google Scholar]
  14. de Bree G. J. , van Leeuwen E. M. , Out T. A. , Jansen H. M. , Jonkers R. E. , van Lier R. A. . ( 2005; ). Selective accumulation of differentiated CD8+ T cells specific for respiratory viruses in the human lung. . J Exp Med 202:, 1433–1442. [CrossRef] [PubMed]
    [Google Scholar]
  15. Doherty P. C. , Topham D. J. , Tripp R. A. , Cardin R. D. , Brooks J. W. , Stevenson P. G. . ( 1997; ). Effector CD4+ and CD8+ T-cell mechanisms in the control of respiratory virus infections. . Immunol Rev 159:, 105–117. [CrossRef] [PubMed]
    [Google Scholar]
  16. Fallarini S. , Paoletti T. , Panza L. , Lombardi G. . ( 2008; ). Alpha-galactosylceramide modulates the induction of indoleamine 2,3-dioxygenase in antigen presenting cells. . Biochem Pharmacol 76:, 738–750. [CrossRef] [PubMed]
    [Google Scholar]
  17. Fallarino F. , Grohmann U. , Vacca C. , Bianchi R. , Orabona C. , Spreca A. , Fioretti M. C. , Puccetti P. . ( 2002; ). T cell apoptosis by tryptophan catabolism. . Cell Death Differ 9:, 1069–1077. [CrossRef] [PubMed]
    [Google Scholar]
  18. Fallarino F. , Grohmann U. , You S. , McGrath B. C. , Cavener D. R. , Vacca C. , Orabona C. , Bianchi R. , Belladonna M. L. . & other authors ( 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.[PubMed] [CrossRef]
    [Google Scholar]
  19. Favre D. , Mold J. , Hunt P. W. , Kanwar B. , Loke P. , Seu L. , Barbour J. D. , Lowe M. M. , Jayawardene A. . & other authors ( 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. [CrossRef] [PubMed]
    [Google Scholar]
  20. Fiore A. E. , Uyeki T. M. , Broder K. , Finelli L. , Euler G. L. , Singleton J. A. , Iskander J. K. , Wortley P. M. , Shay D. K. . & other authors ( 2010; ). Prevention and control of influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2010. . MMWR Recomm Rep 59: (RR-8), 1–62.[PubMed]
    [Google Scholar]
  21. Flynn K. J. , Belz G. T. , Altman J. D. , Ahmed R. , Woodland D. L. , Doherty P. C. . ( 1998; ). Virus-specific CD8+ T cells in primary and secondary influenza pneumonia. . Immunity 8:, 683–691. [CrossRef] [PubMed]
    [Google Scholar]
  22. Frumento G. , Rotondo R. , Tonetti M. , Damonte G. , Benatti U. , Ferrara G. B. . ( 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. [CrossRef] [PubMed]
    [Google Scholar]
  23. Grohmann U. , Fallarino F. , Puccetti P. . ( 2003; ). Tolerance, DCs and tryptophan: much ado about IDO. . Trends Immunol 24:, 242–248. [CrossRef] [PubMed]
    [Google Scholar]
  24. Guillonneau C. , Mintern J. D. , Hubert F. X. , Hurt A. C. , Besra G. S. , Porcelli S. , Barr I. G. , Doherty P. C. , Godfrey D. I. , Turner S. J. . ( 2009; ). Combined NKT cell activation and influenza virus vaccination boosts memory CTL generation and protective immunity. . Proc Natl Acad Sci U S A 106:, 3330–3335. [CrossRef] [PubMed]
    [Google Scholar]
  25. Gupta S. L. , Carlin J. M. , Pyati P. , Dai W. , Pfefferkorn E. R. , Murphy M. J. Jr . ( 1994; ). Antiparasitic and antiproliferative effects of indoleamine 2,3-dioxygenase enzyme expression in human fibroblasts. . Infect Immun 62:, 2277–2284.[PubMed]
    [Google Scholar]
  26. Hayashi T. , Mo J. H. , Gong X. , Rossetto C. , Jang A. , Beck L. , Elliott G. I. , Kufareva I. , Abagyan R. . & other authors ( 2007; ). 3-Hydroxyanthranilic acid inhibits PDK1 activation and suppresses experimental asthma by inducing T cell apoptosis. . Proc Natl Acad Sci U S A 104:, 18619–18624. [CrossRef] [PubMed]
    [Google Scholar]
  27. Hirata F. , Hayaishi O. . ( 1975; ). Studies on indoleamine 2,3-dioxygenase. I. Superoxide anion as substrate. . J Biol Chem 250:, 5960–5966.[PubMed]
    [Google Scholar]
  28. Hwu P. , Du M. X. , Lapointe R. , Do M. , Taylor M. W. , Young H. A. . ( 2000; ). Indoleamine 2,3-dioxygenase production by human dendritic cells results in the inhibition of T cell proliferation. . J Immunol 164:, 3596–3599.[PubMed] [CrossRef]
    [Google Scholar]
  29. Jacoby D. B. , Choi A. M. . ( 1994; ). Influenza virus induces expression of antioxidant genes in human epithelial cells. . Free Radic Biol Med 16:, 821–824. [CrossRef] [PubMed]
    [Google Scholar]
  30. Kloetzel P. M. . ( 2001; ). Antigen processing by the proteasome. . Nat Rev Mol Cell Biol 2:, 179–187. [CrossRef] [PubMed]
    [Google Scholar]
  31. Kreijtz J. H. , Fouchier R. A. , Rimmelzwaan G. F. . ( 2011; ). Immune responses to influenza virus infection. . Virus Res 162:, 19–30. [CrossRef] [PubMed]
    [Google Scholar]
  32. La Gruta N. L. , Kedzierska K. , Pang K. , Webby R. , Davenport M. , Chen W. , Turner S. J. , Doherty P. C. . ( 2006; ). A virus-specific CD8+ T cell immunodominance hierarchy determined by antigen dose and precursor frequencies. . Proc Natl Acad Sci U S A 103:, 994–999. [CrossRef] [PubMed]
    [Google Scholar]
  33. La Gruta N. L. , Rothwell W. T. , Cukalac T. , Swan N. G. , Valkenburg S. A. , Kedzierska K. , Thomas P. G. , Doherty P. C. , Turner S. J. . ( 2010; ). Primary CTL response magnitude in mice is determined by the extent of naive T cell recruitment and subsequent clonal expansion. . J Clin Invest 120:, 1885–1894. [CrossRef] [PubMed]
    [Google Scholar]
  34. Laich A. , Neurauter G. , Widner B. , Fuchs D. . ( 2002; ). More rapid method for simultaneous measurement of tryptophan and kynurenine by HPLC. . Clin Chem 48:, 579–581.[PubMed]
    [Google Scholar]
  35. Lee G. K. , Park H. J. , Macleod M. , Chandler P. , Munn D. H. , Mellor A. L. . ( 2002; ). Tryptophan deprivation sensitizes activated T cells to apoptosis prior to cell division. . Immunology 107:, 452–460. [CrossRef] [PubMed]
    [Google Scholar]
  36. Liu Z. , Dai H. , Wan N. , Wang T. , Bertera S. , Trucco M. , Dai Z. . ( 2007; ). Suppression of memory CD8 T cell generation and function by tryptophan catabolism. . J Immunol 178:, 4260–4266.[PubMed] [CrossRef]
    [Google Scholar]
  37. Makala L. H. , Baban B. , Lemos H. , El-Awady A. R. , Chandler P. R. , Hou D. Y. , Munn D. H. , Mellor A. L. . ( 2011; ). Leishmania major attenuates host immunity by stimulating local indoleamine 2,3-dioxygenase expression. . J Infect Dis 203:, 715–725. [CrossRef] [PubMed]
    [Google Scholar]
  38. Matrosovich M. , Matrosovich T. , Garten W. , Klenk H. D. . ( 2006; ). New low-viscosity overlay medium for viral plaque assays. . Virol J 3:, 63. [CrossRef] [PubMed]
    [Google Scholar]
  39. Mueller S. N. , Langley W. A. , Carnero E. , García-Sastre A. , Ahmed R. . ( 2010; ). Immunization with live attenuated influenza viruses that express altered NS1 proteins results in potent and protective memory CD8+ T-cell responses. . J Virol 84:, 1847–1855. [CrossRef] [PubMed]
    [Google Scholar]
  40. Munn D. H. , Zhou M. , Attwood J. T. , Bondarev I. , Conway S. J. , Marshall B. , Brown C. , Mellor A. L. . ( 1998; ). Prevention of allogeneic fetal rejection by tryptophan catabolism. . Science 281:, 1191–1193. [CrossRef] [PubMed]
    [Google Scholar]
  41. Munn D. H. , Shafizadeh E. , Attwood J. T. , Bondarev I. , Pashine A. , Mellor A. L. . ( 1999; ). Inhibition of T cell proliferation by macrophage tryptophan catabolism. . J Exp Med 189:, 1363–1372. [CrossRef] [PubMed]
    [Google Scholar]
  42. Munn D. H. , Sharma M. D. , Baban B. , Harding H. P. , Zhang Y. , Ron D. , Mellor A. L. . ( 2005; ). GCN2 kinase in T cells mediates proliferative arrest and anergy induction in response to indoleamine 2,3-dioxygenase. . Immunity 22:, 633–642. [CrossRef] [PubMed]
    [Google Scholar]
  43. Murakami Y. , Hoshi M. , Hara A. , Takemura M. , Arioka Y. , Yamamoto Y. , Matsunami H. , Funato T. , Seishima M. , Saito K. . ( 2012; ). Inhibition of increased indoleamine 2,3-dioxygenase activity attenuates Toxoplasma gondii replication in the lung during acute infection. . Cytokine 59:, 245–251. [CrossRef] [PubMed]
    [Google Scholar]
  44. Oshansky C. M. , Thomas P. G. . ( 2012; ). The human side of influenza. . J Leukoc Biol 92:, 83–96. [CrossRef] [PubMed]
    [Google Scholar]
  45. Roberts A. D. , Ely K. H. , Woodland D. L. . ( 2005; ). Differential contributions of central and effector memory T cells to recall responses. . J Exp Med 202:, 123–133. [CrossRef] [PubMed]
    [Google Scholar]
  46. Sharma M. D. , Baban B. , Chandler P. , Hou D. Y. , Singh N. , Yagita H. , Azuma M. , Blazar B. R. , Mellor A. L. , Munn D. H. . ( 2007; ). Plasmacytoid dendritic cells from mouse tumor-draining lymph nodes directly activate mature Tregs via indoleamine 2,3-dioxygenase. . J Clin Invest 117:, 2570–2582. [CrossRef] [PubMed]
    [Google Scholar]
  47. Tanoka K. , Kasahara M. . ( 1998; ). The MHC class I ligand-generating system: roles of immunoproteasomes and the interferon-gamma-inducible proteasome activator PA28. . Immunol Rev 163:, 161–176. [CrossRef] [PubMed]
    [Google Scholar]
  48. Taylor P. M. , Askonas B. A. . ( 1986; ). Influenza nucleoprotein-specific cytotoxic T-cell clones are protective in vivo. . Immunology 58:, 417–420.[PubMed]
    [Google Scholar]
  49. Terness P. , Bauer T. M. , 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. [CrossRef] [PubMed]
    [Google Scholar]
  50. Thomas P. G. , Keating R. , Hulse-Post D. J. , Doherty P. C. . ( 2006; ). Cell-mediated protection in influenza infection. . Emerg Infect Dis 12:, 48–54. [CrossRef] [PubMed]
    [Google Scholar]
  51. Uyttenhove C. , Pilotte L. , Théate I. , Stroobant V. , Colau D. , Parmentier N. , Boon T. , Van den Eynde B. J. . ( 2003; ). Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase. . Nat Med 9:, 1269–1274. [CrossRef] [PubMed]
    [Google Scholar]
  52. Wainwright D. A. , Balyasnikova I. V. , Chang A. L. , Ahmed A. U. , Moon K. S. , Auffinger B. , Tobias A. L. , Han Y. , Lesniak M. S. . ( 2012; ). IDO expression in brain tumors increases the recruitment of regulatory T cells and negatively impacts survival. . Clin Cancer Res 18:, 6110–6121. [CrossRef] [PubMed]
    [Google Scholar]
  53. Wilkinson T. M. , Li C. K. , Chui C. S. , Huang A. K. , Perkins M. , Liebner J. C. , Lambkin-Williams R. , Gilbert A. , Oxford J. . & other authors ( 2012; ). Preexisting influenza-specific CD4+ T cells correlate with disease protection against influenza challenge in humans. . Nat Med 18:, 274–280. [CrossRef] [PubMed]
    [Google Scholar]
  54. Yang H. J. , Yen M. C. , Lin C. C. , Lin C. M. , Chen Y. L. , Weng T. Y. , Huang T. T. , Wu C. L. , Lai M. D. . ( 2010; ). A combination of the metabolic enzyme inhibitor APO866 and the immune adjuvant L-1-methyl tryptophan induces additive antitumor activity. . Exp Biol Med (Maywood) 235:, 869–876. [CrossRef] [PubMed]
    [Google Scholar]
  55. Yoshida R. , Urade Y. , Tokuda M. , Hayaishi O. . ( 1979; ). Induction of indoleamine 2,3-dioxygenase in mouse lung during virus infection. . Proc Natl Acad Sci U S A 76:, 4084–4086. [CrossRef] [PubMed]
    [Google Scholar]
  56. Zhong W. , Marshal D. , Coleclough C. , Woodland D. L. . ( 2000; ). CD4+ T cell priming accelerates the clearance of Sendai virus in mice, but has a negative effect on CD8+ T cell memory. . J Immunol 164:, 3274–3282. [CrossRef] [PubMed]
    [Google Scholar]
  57. Zhong W. , Reche P. A. , Lai C. C. , Reinhold B. , Reinherz E. L. . ( 2003; ). Genome-wide characterization of a viral cytotoxic T lymphocyte epitope repertoire. . J Biol Chem 278:, 45135–45144. [CrossRef] [PubMed]
    [Google Scholar]
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