Gamma interferon-induced inhibition of Toxoplasma gondii in astrocytes is mediated by IGTP
Gamma interferon-induced inhibition of Toxoplasma gondii in astrocytes is mediated by IGTP
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DOI：
10.1128/iai.69.9.5573-5576.2001
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发表时间：
2001-09-01
影响因子：
3.1
通讯作者：
Weiss, LM
中科院分区：
文献类型：
--
作者：
Halonen, SK;Taylor, GA;Weiss, LM
弓形虫是一种重要的中枢神经系统病原体，可引起艾滋病患者严重且往往致命的脑炎。γ干扰素（IFN-γ）是防止脑内弓形虫脑炎再激活的主要细胞因子。小胶质细胞是重要的IFN-γ激活的效应细胞，控制T.弓形虫通过一氧化氮（NO）介导的机制在大脑中。IFN-γ还可以激活星形胶质细胞，抑制T.刚地以往的研究发现，在小鼠星形胶质细胞的机制是独立的NO和所有其他已知的抗弓形虫机制。在这项研究中，我们研究了最近发现的IFN-γ调节基因IGTP在IFN-γ抑制T细胞中的作用。鼠星形胶质细胞中的弓形虫。从IGTP缺陷小鼠培养原代星形胶质细胞，用IFN-γ处理，然后测试抗弓形虫活性。在野生型星形胶质细胞T. IFN-γ显著抑制弓形虫的生长，而在IGTP缺陷小鼠的星形胶质细胞中，IFN-γ没有引起显著的生长抑制。免疫印迹分析证实，IFN-T在24小时内诱导野生型小鼠星形胶质细胞中显著水平的IGTP。这些结果表明，IGTP在IFN-γ诱导的T.鼠星形胶质细胞中的弓形虫。
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-T 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.