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 e ndothelial cells (HBMEC) to interact with Toxoplasma gondii. We found that stimulation of HBMEC with gamma interferon (IFN-gamma) resulted in the indu ction of toxoplasmostasis. The capacity of HBMEC to restrict Toxoplasma gro wth after IFN-gamma stimulation was enhanced in the presence of tumor necro sis 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 toxoplasmostasi s. We therefore conclude that IDO induction contributed to the antiparasiti c effector mechanism inducible in HBMEC by IFN-gamma and TNF-alpha.