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

• Published in: Infection and immunity 2001-10, Vol.69 (10), p.6527-6531
• Main Authors: DÄUBENER, Walter, SPORS, Birgit, HUCKE, Christian, ADAM, Rüdiger, STINS, Monique, KWANG SIK KIM, SCHROTEN, Horst
• Format: Article
• Language: English
• Subjects: Adult; Animals; Bacteriology; Biological and medical sciences; Brain - blood supply; Capillaries - cytology; Cells, Cultured; Endothelium, Vascular - cytology; Enzyme Activation; Enzyme Induction; Female; Fundamental and applied biological sciences. Psychology; Fungal and Parasitic Infections; Genetics; Humans; Indoleamine 2,3-Dioxygenase; Indoleamine-Pyrrole 2,3,-Dioxygenase; Interferon-gamma - metabolism; Interferon-gamma - pharmacology; Microbiology; Nitric Oxide Synthase - genetics; Nitric Oxide Synthase Type II; Pathogenicity, virulence, toxins, bacteriocins, pyrogens, host-bacteria relations, miscellaneous strains; Toxoplasma - drug effects; Toxoplasma - growth & development; Toxoplasma gondii; Tryptophan Oxygenase - genetics; Tryptophan Oxygenase - metabolism; tumor necrosis factor- alpha; Tumor Necrosis Factor-alpha - metabolism; Tumor Necrosis Factor-alpha - pharmacology
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.69.10.6527-6531.2001

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.