Inhibition of indoleamine 2,3-dioxygenase in human macrophages inhibits interferon-γ-induced bacteriostasis but does not abrogate toxoplasmastasis
✍ Scribed by Colin R. MacKenzie; Ralf Langen; Osamu Takikawa; Walter Däubener
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 142 KB
- Volume
- 29
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
Induction of indoleamine 2,3-dioxygenase (IDO) by IFN-+ results in growth inhibition of Toxoplasma and Chlamydia spp. as well as tumor cells. This is caused by the degradation, and therefore depletion, of L-tryptophan necessary for cell protein synthesis. Human macrophages stimulated with IFN-+ express IDO and inhibit the growth of intracellular toxoplasma and chlamydia as well as that of extracellular bacteria such as group B streptococci. Here we describe experiments in which the L-tryptophan analog, 6-chloro-DL-tryptophan (CDLT) caused a dose-dependent inhibition in the IFN-+ -induced IDO-mediated L-tryptophan degradation in monocyte-derived macrophages and glioblastoma cells. An inhibition of IDO activity of up to 80 % was observed at concentrations of CDLT of 750 ? M. Expression of IDO at this concentration, as shown by Northern blot analysis, was unimpaired. This inhibition of IDO was coupled in glioblastoma cells by a complete abrogation of the IFN-+ -induced toxoplasmastasis in these cells. IDO inhibition by CDLT in human macrophages resulted in a complete abrogation of the IFN-+ -induced growth inhibition of streptococci and staphylococci. In contrast to this, IFN-+ -induced toxoplasmastasis was not inhibited in human macrophages by CDLT-mediated IDO inhibition.