The missing link between indoleamine 2,3-dioxygenase mediated antibacterial and immunoregulatory effects
| Autor: | Kathrin Heseler, K. Spekker, Walter Däubener, Anika Müller, Silvia K. Schmidt, Colin R. MacKenzie |
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| Rok vydání: | 2009 |
| Předmět: |
Staphylococcus aureus
Time Factors indoleamine 2 3-dioxygenase T-Lymphocytes Biology Microbiology Cell Line chemistry.chemical_compound Enzyme activator Interferon-gamma Interferon Cell Line Tumor interferon-γ medicine Humans Indoleamine-Pyrrole 2 3 -Dioxygenase Interferon gamma Indoleamine 2 3-dioxygenase Cell Proliferation Bacteria Dose-Response Relationship Drug Cell growth Effector Tryptophan T cell Cell Biology Articles kynurenine Enzyme Activation chemistry Biochemistry Molecular Medicine Kynurenine Enterococcus medicine.drug HeLa Cells |
| Zdroj: | Journal of Cellular and Molecular Medicine |
| ISSN: | 1582-4934 |
| Popis: | The interferon (IFN)-gamma-inducible tryptophan degrading enzyme indoleamine 2,3-dioxygenase (IDO) has not only been recognized as a potent antimicrobial effector molecule for the last 25 years but was recently found also to have potent immunoregulatory properties. In this study, we provide evidence that both tryptophan starvation and production of toxic tryptophan metabolites are involved in the immunoregulation mediated by IDO, whereas tryptophan starvation seems to be the only antibacterial effector mechanism. A long-studied controversy in the IDO research field is the seemingly contradictory effect of IDO in the defence against infectious diseases. On the one hand, IFN-gamma-induced IDO activity mediates an antimicrobial effect, while at the same time IDO inhibits T-cell proliferation and IFN-gamma production. Here, we suggest that both effects, dependent on the threshold for tryptophan, cooperate in a reasonable coherence. We found that the minimum concentration of tryptophan required for bacterial growth is 10-40-fold higher than the minimum concentration necessary for T-cell activation. Therefore, we suggest that during the first phase of infection the IDO-mediated tryptophan depletion has a predominantly antimicrobial effect whereas in the next stage, and with ongoing tryptophan degradation, the minimum threshold concentration of tryptophan for T-cell activation is undercut, resulting in an inhibition of T-cell growth and subsequent IDO activation. |
| Databáze: | OpenAIRE |
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