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.
Halonen
S K
SK
Department of Natural Sciences, Mercy College, Dobbs Ferry, New York 10522, USA.
Taylor
G A
GA
Weiss
L M
LM
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000469:parasitology*; D002478:Cells, Cultured; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000502:physiology*; D007371:Interferon-gamma / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D014122:Toxoplasma / Q000187:drug effects* / Q000276:immunology; D016781:Toxoplasmosis, Cerebral / Q000469:parasitology
D007371:Interferon-gamma; D020558:GTP Phosphohydrolases; C101131:Igtp protein, mouse