Toxoplasma gondii glycosylphosphatidylinositols up-regulate major histocompatibility complex (MHC) molecule expression on primary murine macrophages.
Toxoplasma gondii glycosylphosphatidylinositols up-regulate major histocompatibility complex (MHC) molecule expression on primary murine macrophages.
复制标题
DOI：
10.1177/1753425908099936
复制
发表时间：
2009-02-01
期刊：
影响因子：
3.2
通讯作者：
Luder, Carsten G K
中科院分区：
文献类型：
--
作者：
Debierre-Grockiego, Francoise;Molitor, Nicole;Luder, Carsten G K
弓形虫是一种必须的细胞内寄生虫，能够阻断干扰素-γ诱导的主要组织相容性复合体(MHC)I类和II类分子的上调。这有助于寄生虫介导的T细胞反应的逃避。糖基磷脂酰肌醇(GGIs)参与了原生动物寄生虫的致病过程，我们研究了GPI是否与抑制巨噬细胞MHC的表达有关。与在感染活的速殖子的细胞中观察到的阻断相反，弓形虫GPI上调未刺激和干扰素刺激的原代小鼠巨噬细胞表面MHC I类和II类分子。这一效应与GPI增加CD8(+)淋巴细胞抗原呈递的能力有关。弓形虫GPI不激活STAT1，STAT1是参与MHC I类和II类基因转录的因子之一。然而，GPI诱导的MHC-I类上调可被特异性的NF-KB抑制剂SN50所阻断。GPI上调表面MHC分子可能导致宿主免疫系统非感染细胞的清除，有助于弓形虫的免疫逃逸策略。
Toxoplasma gondii is an obligatory intracellular parasite able to block the IFN-gamma-induced up-regulation of major histocompatibility complex (MHC) class I and class II molecules. This facilitates parasite-mediated evasion of T-cell responses. Glycosylphosphatidylinositols (GPIs) are involved in the pathogenicity of protozoan parasites and we investigated if GPIs are responsible for inhibition of MHC expression on macrophages. In contrast to the blockade observed in cells infected with viable tachyzoites, T. gondii GPIs up-regulated MHC class I and class II molecules on the surface of both unstimulated and IFN-gamma-stimulated primary murine macrophages. This effect was correlated to the ability of GPIs to increase the antigen presentation to CD8(+) lymphocytes. T. gondii GPIs did not activate STAT1, one of the factors involved in the transcription of MHC class I and class II genes. However, the GPI-induced MHC class I up-regulation was abrogated by SN50, a specific NF-KB inhibitor. Up-regulation of surface MHC molecules by GPIs may lead to the elimination of non-infected cells of the host immune system, contributing to the immune escape strategy of T. gondii.