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Infection and Immunity, September 2001, p. 5573-5576, Vol. 69, No. 9
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.9.5573-5576.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Gamma Interferon-Induced Inhibition of Toxoplasma gondii in Astrocytes Is Mediated by IGTP

Sandra K. Halonen,1,2 Gregory A. Taylor,3,4 and Louis M. Weiss2,5,*

Department of Natural Sciences, Mercy College, Dobbs Ferry, New York 105221; Departments of Pathology2 and Medicine,5 Albert Einstein College of Medicine, Bronx, New York 10461; Departments of Medicine and Immunology and the Center for the Study of Aging and Human Development, Duke University, Durham, North Carolina 277103; and Geriatric Research, Education, and Clinical Center, Durham VA Medical Center, Durham, North Carolina 277054

Received 29 March 2001/Returned for modification 24 May 2001/Accepted 14 June 2001

Toxoplasma gondii is an important pathogen in the central nervous system, causing a severe and often fatal encephalitis in patients with AIDS. Gamma interferon (IFN-gamma ) is the main cytokine preventing reactivation of Toxoplasma encephalitis in the brain. Microglia are important IFN-gamma -activated effector cells controlling the growth of T. gondii in the brain via a nitric oxide (NO)-mediated mechanism. IFN-gamma can also activate astrocytes to inhibit the growth of T. gondii. Previous studies found that the mechanism in murine astrocytes is independent of NO and all other known anti-Toxoplasma mechanisms. In this study we investigated the role of IGTP, a recently identified IFN-gamma -regulated gene, in IFN-gamma inhibition of T. gondii in murine astrocytes. Primary astrocytes were cultivated from IGTP-deficient mice, treated with IFN-gamma , and then tested for anti-Toxoplasma activity. In wild-type astrocytes T. gondii growth was significantly inhibited by IFN-gamma , whereas in astrocytes from IGTP-deficient mice IFN-gamma did not cause a significant inhibition of growth. Immunoblot analysis confirmed that IFN-gamma induced significant levels of IGTP in wild-type murine astrocytes within 24 h. These results indicate that IGTP plays a central role in the IFN-gamma -induced inhibition of T. gondii in murine astrocytes.

* Corresponding author. Mailing address: Department of Pathology, Division of Parasitology and Tropical Medicine, Albert Einstein College of Medicine, Bronx, NY 10461. Phone: (718) 430-2142. Fax: (718) 430-8543. E-mail: lmweiss{at}aecom.yu.edu.

Infection and Immunity, September 2001, p. 5573-5576, Vol. 69, No. 9
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.9.5573-5576.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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