Diverse mechanisms employed by Toxoplasma gondii to inhibit IFN-γ-induced major histocompatibility complex class II gene expression
Diverse mechanisms employed by Toxoplasma gondii to inhibit IFN-γ-induced major histocompatibility complex class II gene expression
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DOI：
10.1016/j.micinf.2006.02.031
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发表时间：
2006-07-01
影响因子：
5.8
通讯作者：
Lueder, G. K.
中科院分区：
文献类型：
--
作者：
Lang, Christine;Algner, Michaela;Lueder, G. K.
细胞内寄生虫弓形虫能够在免疫活性宿主中建立持续感染，这可能是由不同的免疫逃避机制促进的。本研究用T.弓形虫阻断IFN-γ诱导的主要组织相容性复合体（MHC）II类mRNA和蛋白的上调。热灭活的寄生虫入侵宿主细胞之前，但不抑制T。gondii可消除对MHC II类分子上调的抑制作用。有趣的是，T。弓形虫裂解物（TL）模拟活寄生虫对MHC II类表达的抑制作用。细胞核转位的信号转导子和转录激活子在IFN-γ的反应是正常的，无论是在细胞与TL孵育或感染有活力的寄生虫。转录水平的II类反式激活因子，因此H2-抗体，但减少了两个可行的寄生虫和TL。与此相反，干扰素调节因子-1 mRNA仅在对活T.刚地。荧光素酶报告基因测定证实了活寄生虫和TL对最小或复杂的IFN-γ应答启动子的差异效应。此外，只有TL，而不是可行的寄生虫，强烈诱导海洋巨噬细胞分泌IL-10。而TL也抑制了IL-10缺陷小鼠巨噬细胞中MHC II类分子的表达，野生型巨噬细胞IL-10分泌的增加并不介导MHC II类分子上调的阻断。总之，T.弓形虫采用不同的机制来抑制MHC II类分子的表达，表明这种免疫逃避策略的复杂调节。(c)2006年，Elsevier SAS。All rights reserved.
The intracellular parasite Toxoplasma gondii is able to establish persistent infections in immunocompetent hosts and this may be facilitated by different immune evasion mechanisms. In the present study, we describe that infection of marine monocyte/macrophage RAW 264.7 cells with T. gondii blocks the IFN-gamma-induced upregulation of major histocompatibility complex (MHC) class II mRNAs and proteins. Heat inactivation of the parasites prior to host cell invasion, but not inhibition of the intracellular replication of T. gondii abolished the inhibition of MHC class II upregulation. Interestingly, a T. gondii lysate (TL) mimicked the inhibitory effect of viable parasites on MHC class II expression. Nuclear translocation of the signal transducer and activator of transcription in response to IFN-gamma were normal both in cells incubated with TL or infected with viable parasites. Transcript levels of the class II transactivator and consequently H2-Ab were nevertheless diminished by both viable parasites and TL. In contrast, interferon regulatory factor-1 mRNA was only decreased in response to viable T. gondii. Luciferase reporter assays confirmed differential effects of viable parasites and TL on minimal or complex IFN-gamma-responsive promoters. Furthermore, only TL, and not viable parasites, strongly induced the secretion of IL-10 by marine macrophages. Whereas TL also inhibited MHC class II expression in macrophages from IL-10-deficient mice, increased IL-10 secretion by wild type macrophages did not mediate the block in MHC class II upregulation. In conclusion, T. gondii employs different mechanisms to inhibit MHC class II expression, suggesting a complex regulation of this immune evasion strategy. (c) 2006 Elsevier SAS. All rights reserved.