Gamma interferon-induced inhibition of Toxoplasma gondii in astrocytes is mediated by IGTP.
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.
Duke Scholars
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- Toxoplasmosis, Cerebral
- Toxoplasma
- Microbiology
- Mice, Inbred C57BL
- Mice
- Interferon-gamma
- GTP Phosphohydrolases
- Cells, Cultured
- Astrocytes
- Animals
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Toxoplasmosis, Cerebral
- Toxoplasma
- Microbiology
- Mice, Inbred C57BL
- Mice
- Interferon-gamma
- GTP Phosphohydrolases
- Cells, Cultured
- Astrocytes
- Animals