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Infection and Immunity, October 2001, p. 6527-6531, Vol. 69, No. 10
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.10.6527-6531.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Restriction of Toxoplasma gondii Growth in Human Brain Microvascular Endothelial Cells by Activation of Indoleamine 2,3-Dioxygenase

Walter Däubener,1,* Birgit Spors,2 Christian Hucke,1 Rüdiger Adam,2 Monique Stins,3 Kwang Sik Kim,3 and Horst Schroten2

Institute for Medical Microbiology and Virology1 and University Children's Hospital,2 Düsseldorf, Germany, and Department of Pediatrics, Division of Infectious Diseases, Children's Hospital, Johns Hopkins University, Baltimore, Maryland3

Received 20 February 2001/Returned for modification 4 April 2001/Accepted 10 July 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 .

* Corresponding author. Mailing address: Institut für Medizinische Mikrobiologie und Virologie, Heinrich-Heine-Universität Düsseldorf, Postfach 101007, 40001 Düsseldorf, Germany. Phone: 49-211-811-2464. Fax: 49-211-811-5323. E-mail: daeubene{at}uni-duesseldorf.de.

Infection and Immunity, October 2001, p. 6527-6531, Vol. 69, No. 10
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.10.6527-6531.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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