Restriction of Toxoplasma gondii growth in human brain microvascular endothelial cells by activation of indoleamine 2,3-dioxygenase

被引:95
作者
Däubener, W
Spors, B
Hucke, C
Adam, R
Stins, M
Kim, KS
Schroten, H
机构
[1] Univ Dusseldorf, Inst Med Mikrobiol & Virol, D-40001 Dusseldorf, Germany
[2] Univ Dusseldorf, Childrens Hosp, D-4000 Dusseldorf, Germany
[3] Johns Hopkins Univ, Childrens Hosp, Dept Pediat, Div Infect Dis, Baltimore, MD USA
关键词
D O I
10.1128/IAI.69.10.6527-6531.2001
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
One of the first steps in the development of cerebral toxoplasmosis is the penetration of the blood-brain barrier, which is comprised of microvascular endothelial cells. We examined the capacity of human brain microvascular endothelial cells (HBMEC) to interact with Toxoplasma gondii. We found that stimulation of HBMEC with gamma interferon (IFN-gamma) resulted in the induction of toxoplasmostasis. The capacity of HBMEC to restrict Toxoplasma growth after IFN-gamma stimulation was enhanced in the presence of tumor necrosis factor alpha (TNF-alpha). In addition, we found that IFN-gamma induced a strong induction of indoleamine 2,3-dioxygenase (IDO) activity in HBNMC, and this enzyme activity was enhanced by costimulation with TNF-alpha. The addition of excess amounts of tryptophan to the HBMEC cultures resulted in a complete abrogation of the IFN-gamma -TNF-alpha -mediated toxoplasmostasis. We therefore conclude that IDO induction contributed to the antiparasitic effector mechanism inducible in HBMEC by IFN-gamma and TNF-alpha.
引用
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页码:6527 / 6531
页数:5
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