Debierre-Grockiego Françoise, Molitor Nicole, Schwarz Ralph T, Lüder Carsten G K
Institut für Virologie, AG Parasitologie, Philipps Universität Marburg, Marburg, Germany.
Innate Immun. 2009 Feb;15(1):25-32. doi: 10.1177/1753425908099936.
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.
刚地弓形虫是一种专性细胞内寄生虫，能够阻断γ干扰素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逃避T细胞反应。糖基磷脂酰肌醇（GPI）参与原生动物寄生虫的致病性，我们研究了GPI是否负责抑制巨噬细胞上MHC的表达。与感染活速殖子的细胞中观察到的阻断情况相反，刚地弓形虫GPI上调了未刺激和经γ干扰素刺激的原代小鼠巨噬细胞表面的MHC I类和II类分子。这种效应与GPI增加向CD8(+)淋巴细胞呈递抗原的能力相关。刚地弓形虫GPI未激活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类上调被特异性NF-κB抑制剂SN50消除。GPI对表面MHC分子的上调可能导致宿主免疫系统未感染细胞的清除，这有助于刚地弓形虫的免疫逃逸策略。
