Restriction of Toxoplasma gondii growth in human brain microvascular endothelial cells by activation of indoleamine 2,3-dioxygenase.
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 HBMEC, 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.
Däubener
W
W
Institute for Medical Microbiology and Virology, Düsseldorf, Germany. daeubene@uni-duesseldorf.de
Spors
B
B
Hucke
C
C
Adam
R
R
Stins
M
M
Kim
K S
KS
Schroten
H
H
D000328:Adult; D000818:Animals; D001921:Brain / Q000098:blood supply*; D002196:Capillaries / Q000166:cytology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology; D004789:Enzyme Activation; D004790:Enzyme Induction; D005260:Female; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D014122:Toxoplasma / Q000187:drug effects / Q000254:growth & development*; D014366:Tryptophan Oxygenase / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D014366:Tryptophan Oxygenase; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II