Skip to main content

Ifn-γ Activated Indoleamine 2,3-Dioxygenase Activity in Human Cells is an Antiparasitic and an Antibacterial Effector Mechanism

  • Chapter
Tryptophan, Serotonin, and Melatonin

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 467))

Abstract

In nearly all human cells IFN-γ Stimulation leads to an activation of indoleamine 2,3-dioxygenase (IDO) activity, which is responsible for anti-toxoplasma and anti-chlamydia effects. We have recently shown that IDO activation is also a defense mechanism against extracellular β-hemolytic streptococci groups A,B,C and G in human glioblastoma cells, fibroblasts and macrophages. Similar effects were also seen with enterococci and in approximately 65% of staphylococci tested, including multiresistant strains of both species. In addition, we have found that IDO activity is differentially regulated in different cells. For example we have found that TNF-α enhances IFN-γ induced IDO activity and antimicrobial effect in human glioblastoma cells whereas both IFN-γ mediated effects were blocked by TNF-α as well as by IL-1 in a human uroepithelial cell line. We were able to show that the IL-1 and TNF-α mediated inhibition of IFN-γ-induced IDO activity in uroepithelial cells is due to stimulation of inducible nitric oxide synthase. In human astrocytoma cells, IL-1 and TNF-α did not inhibit IDO activity and in concordance with this finding these cells did not show a detectable nitric oxide production.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Byrne, J.I., Lehmann, L.K., and Landry, G.J., 1986, Induction of tryptophan catabolism is the mechanism for gamma-interferon-mediated inhibition of intracellular Chlamydia psittaci replication in T24 cells, Infect. Immun. 53:347–351.

    PubMed  CAS  Google Scholar 

  • Däubener, W. and Hadding, U., 1997, Cellular immune reactions directed against Toxoplasma gondii with special emphasis on the central nervous system, Med. Microbiol. Immunol. 185:195–206.

    Article  PubMed  Google Scholar 

  • Däubener, W., Nockemann, S., Gutsche, M., and Hadding, U., 1995, Heparin inhibits the antiparasitic and immune modulatory effects of human recombinant interferon-γ, Eur. J. Immunol. 25:688–692.

    Article  PubMed  Google Scholar 

  • Däubener, W., Pilz, K., Seghrouchni-Zennati, S., Bilzer, T., Fischer, H.G., and Hadding, U., 1993, Induction of toxoplasmostasis in a human glioblastoma by interferon-γ, J. Neuroimmunol. 43:31–38.

    Article  PubMed  Google Scholar 

  • Farrar, M.A. and Schreiber, R.D., 1993, The molecular cell biology of interferon-γ and its receptor, Annu. Rev. Immunol. 11:571–611.

    Article  PubMed  CAS  Google Scholar 

  • Habara-Ohkubo, A., Shirahata, T., Takikawa, O., and Yoshida, R., 1993, Establishment of an antitoxoplasma state by stable expression of mouse indoleamine 2,3-dioxygenase, Infect. Immun. 61:1810–1813.

    PubMed  CAS  Google Scholar 

  • Hayaishi, O., Hirata, F., Ohnishi, T., Henry, J.P., Rosenthal, I., and Katoh, A., 1988, Indoleamine 2,3-dioxygenase, J. Biol. Chem. 252:3548–3550.

    Google Scholar 

  • Heyes, M.P., Achim, C.L., Wiley, C.A., Major, E.O., Saito, K., and Markey, S.P., 1996, Human microglia convert L-tryptophan into the neurotoxin quinolinic acid, J. Biochem. 320:595–597.

    CAS  Google Scholar 

  • Lee, S.C., Dickson, D.W., Brosnan, C.F., and Cassadevall, 1994, Human astrocytes inhibit Cryptococcus neoformans growth by a nitric oxide-mediated mechanism, J. Exp. Med. 180:365–369.

    Article  PubMed  CAS  Google Scholar 

  • Liew, F.Y. and Cox, F.E.G., 1991, Nonspecific defence mechanism: the role of nitric oxide, Immunol. Today 12:A17–21.

    Article  PubMed  CAS  Google Scholar 

  • Liew, F.Y., Li, Y., Moss, D., Rogers, M.V., and Moncada, S., 1991, Resistance to Leishmania major infection correlates with the induction of nitric oxide synthase in murine macrophages, Eur. J. Immunol. 21:3009–3014.

    Article  PubMed  CAS  Google Scholar 

  • MacKenzie, C.R., Hadding, U., and Däubener, W., 1998, Interferon-γ induced activation of indoleamine 2,3-dioxygenase in cord blood monocyte derived macrophages inhibits the growth of group B streptococci, J. Infect. Dis. 178:875–878.

    Article  PubMed  CAS  Google Scholar 

  • MacKenzie, C.R., Willberg, C.B., and Däubener, W., 1998, Inhibition of group B streptococcal growth by IFN-γ activated human glioblastoma cells, J. Neuroimmunol. 89:191–197.

    Article  PubMed  CAS  Google Scholar 

  • Meda, L., Cassatella, M.A., Szendrei G.I., Otvos, L., Baron, P., Villalba, M., Ferrari, D, and Rossi, F., 1995, Activation of microglial cells by b-amyloid protein and interferon-γ, Nature. 374:647–650.

    Article  PubMed  CAS  Google Scholar 

  • Mellio, G., Cox, G.W., Radzioch, D., and Varesio, L., 1993, Picolinic acid, a catabolite of L-tryptophan, is a costimulus for the induction of reactive nitrogen intermediate production in murine macrophages, J. Immunol. 150:4031–4040.

    Google Scholar 

  • Murray, H.W., Szuro-Sudol, A., Wellner, D., Oca, M.J., Granger, A.M., Libby, D.M., Rothermel, C.D., and Rubin, B.Y., 1989, Role of tryptophan degradation in respiratory burst-independent antimicrobial activity of gamma interferon-stimulated human macrophages, Infect. Immun. 57:845–849.

    PubMed  CAS  Google Scholar 

  • Murray H.W. and Teitelbaum, R.F., 1992, L-arginine-dependent reactive nitrogen intermediates and the antimicrobial effect of activated human mononuclear phagocytes, J. Infect. Dis. 165:513–517.

    Article  PubMed  CAS  Google Scholar 

  • Nagineni, C.N., Pardhasaradhi, K., Martins, M.C., Detrick, B., and Hooks, J.J., 1996, Mechanisms of inter-feron-induced inhibition of Toxoplasma gondii replication in human retinal pigment epithelial cells, Infect. Immun. 64:4188–4196.

    PubMed  CAS  Google Scholar 

  • Ozaki, Y., Edelstein, M.P., and Duch, D.S., 1988, Induction of indolamine 2,3-dioxygenase: A mechanism of the antitumor activity of interferon-γ, Proc. Natl. Acad. Sci. USA. 85:1242–1246.

    Article  PubMed  CAS  Google Scholar 

  • Peterson, P.K., Gekker, G., Hu, S., and Chao, C.C., 1995, Human astrocytes inhibit intracellular multiplication of Toxoplasma gondii by a nitric oxide-mediated mechanism, J. Infect. Dis. 171:516–518.

    Article  PubMed  CAS  Google Scholar 

  • Pfefferkorn, E.R., 1984, Interferon-γ blocks the growth of Toxoplasma gondii in human fibroblasts by inducing the host cells to degradate tryptophan. Proc. Natl. Acad. Sci. USA. 81:908–912.

    Article  PubMed  CAS  Google Scholar 

  • Roilides, E., Uhlig, K., Venzon, D., Pizzo, P.A., and Walsh, T.J., 1993, Enhancement of oxidative response and damage caused by human neutrophils to Aspergillus fumigatus hyphae by granulocyte colony stimulating factor and gamma interferon, Infect. Immun. 61:1185–1193.

    PubMed  CAS  Google Scholar 

  • Schneemann, M., Schoedon, G., Hofer, S., Blau, N., Guerro, L., and Schaffner, A., 1993, Nitric oxide synthase is not a constituent of the antimicrobial armature of human mononuclear phagocytes, J. Infect. Dis. 167:1358–1363.

    Article  PubMed  CAS  Google Scholar 

  • Shimizu, T., Nomiyama, S., Hirata, F., and Hayaishi, O., 1978, Indoleamine 2,3-dioxygenase, J. Biol. Chem. 253:4700–4706.

    PubMed  CAS  Google Scholar 

  • Sibley, D., Messina, M., and Niesman, I.R., 1994, Stable DNA transformation in the obligate intracellular parasite Toxoplasma gondii by complementation of tryptophan auxotrophy, Proc. Natl. Acad. Sci. USA. 91:5508–5512.

    Article  PubMed  CAS  Google Scholar 

  • Stone, T.W., 1993, Neuropharmacology of quinolonic and kynurenic acids, Pharmacol. Rev. 45:309–379.

    PubMed  CAS  Google Scholar 

  • Taylor, M.W. and Feng, G., 1991, Relationship between interferon-γ, indoleamine 2,3-dioxygenase, and tryptophan catabolism, J. FASEB. 5:2516–2522. AR308.

    CAS  Google Scholar 

  • Thomas, S.M., Garrity, L.F., Brandt, C.R., Schobert, C.S., Feng, G.S., Taylor, M.W, Carlin, J.M., and Byrne, G.I., 1993, IFN-γ mediated antimicrobial response, J. Immunol. 150:5529–5534.

    PubMed  CAS  Google Scholar 

  • Thomas, S.R., Mohr, D., and Stocker, R., 1994, Nitric oxide inhibits indoleamine 2,3-dioxygenase activity in interferon-γ primed mononuclear phagocytes, J. Biol. Chem. 269:14457–14464.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1999 Springer Science+Business Media New York

About this chapter

Cite this chapter

Däubener, W., MacKenzie, C.R. (1999). Ifn-γ Activated Indoleamine 2,3-Dioxygenase Activity in Human Cells is an Antiparasitic and an Antibacterial Effector Mechanism. In: Huether, G., Kochen, W., Simat, T.J., Steinhart, H. (eds) Tryptophan, Serotonin, and Melatonin. Advances in Experimental Medicine and Biology, vol 467. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4709-9_64

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-4709-9_64

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-7133-5

  • Online ISBN: 978-1-4615-4709-9

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics