Toxoplasma gondii down-regulates MHC class II gene expression and antigen presentation by murine macrophages via interference with nuclear translocation of STAT1α
Toxoplasma gondii down-regulates MHC class II gene expression and antigen presentation by murine macrophages via interference with nuclear translocation of STAT1α
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DOI：
10.1002/1521-4141(200105)31:5
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发表时间：
2001-05-01
影响因子：
5.4
通讯作者：
Gross, U
中科院分区：
文献类型：
--
作者：
Lüder, CGK;Walter, W;Gross, U
专性细胞内原生动物寄生虫刚地弓形虫能够在人类和动物宿主中建立持续感染。我们最近表明，弓形虫下调ifn - γ诱导的小鼠骨髓源性巨噬细胞（BMM phi）中MHC类II的表达。如本研究所示，ifn - γ激活的小鼠BMM phi向CD4(+) T细胞杂交瘤呈送卵白蛋白的能力被弓形虫剂量依赖性地抑制。弓形虫显著下调ifn - γ诱导的H2-Aa、H2-Ab、H2-Eb、H2-Ma、H2-Mb、H2-Oa和不变链转录本的上调。此外，II类反激活因子和干扰素调节因子-1的mRNA水平显著降低。电迁移转移实验表明，刚地弓形虫感染后，核提取物与ifn - γ激活位点的结合活性降低，表明寄生虫干扰了ifn - γ诱导的信号传导。然而，弓形虫并没有减少ifn - γ - α链和转录信号传导激活因子（STAT） 1 α的酪氨酸磷酸化，也没有减少ifn - γ - α的表达。免疫荧光显微镜和亚细胞分离分析显示，感染后ifn - γ诱导的STAT1 α核易位受到抑制。总之，这种微生物干扰MHC II类基因表达的新机制可能有助于弓形虫的细胞内存活和持续感染的建立。
The obligate intracellular protozoan parasite Toxoplasma gondii is able to establish persistent infections within human and animal hosts. We have shown recently that T. gondii downregulates IFN-gamma -induced MHC class II expression in murine bone marrow-derived macrophages (BMM phi). As shown in this study, the capacity of IFN-gamma -activated murine BMM phi to present ovalbumin to CD4(+) T cell hybridomas was dose-dependently inhibited by T. gondii. IFN-gamma -induced up-regulation of H2-Aa, H2-Ab, H2-Eb, H2-Ma, H2-Mb, H2-Oa and invariant chain transcripts was prominently down-regulated by T. gondii. Furthermore, mRNA levels of class II transactivator and interferon-regulatory factor-1 were significantly diminished. Electromobility shift assays demonstrated a decrease in the binding activity of nuclear extracts to the IFN-gamma -activated site after infection with T gondii, indicating parasitic interference with IFN-gamma -induced signaling. However, neither the expression of the IFN-gammaR nor the IFN-gamma -induced tyrosine phosphorylation of IFN-gammaR alpha chain and signal transducer and activator of transcription (STAT) 1 alpha was diminished by T. gondii. IFN-gamma -induced nuclear translocation of STAT1 alpha was nevertheless inhibited after infection as demonstrated by immunofluorescence microscopy and subcellular fractionation analyses. In conclusion, this novel mechanism of microbial interference with MHC class II gene expression may contribute to intracellular survival and establishment of persistent infection with T:gondii.