State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China; Nanchong Key Laboratory of Disease Prevention, Control and Detection in Livestock and Poultry, Nanchong Vocational and Technical College, Nanchong, China.
Exp Mol Pathol. 2021 Dec;123:104684. doi: 10.1016/j.yexmp.2021.104684. Epub 2021 Sep 20.
The immunoproteasomes are specific proteasomes that clear oxidant-damaged proteins under inflammatory conditions in various diseases. Toxoplasma gondii (T. gondii) infects the central nervous system and causeencephalitis. However, the relationship between the immunoproteasomes and brain inflammation during T. gondii infection is not well characterized. In this study, we established an in vivo mouse model of T. gondii PLK strain infection via intraperitoneal injection and evaluated the expression of immunoproteasome subunits in the brains of infected mice. The results demonstrated that first, pathological changes in the brains of infected mice increase in severity over time. Second, following T. gondii infection, activated microglia and astrocytes undergo a series of functional alterations and morphological transformations, including proliferation and migration. Third, T. gondii infection induces expression of inflammatory cytokines, including IFN-γ, IL-1β, TNF-α, and IL-6. Fourth, the immunoproteasome subunits low-molecular-weight polypeptide 2 (LMP2), LMP7, and LMP10 mRNA and protein levels are significantly upregulated in T. gondii-infected mouse brains, as shown by RT-qPCR and western blot analysis, compared with that in vehicle-treated brains, and their expression is localized in the microglia, astrocytes, and neurons of T. gondii-infected brains, as determined via immunofluorescence staining. Furthermore, the western blot mean gray value for the immunoproteasome subunits and the positive microglia and astrocyte immunohistochemical signals in the brains of T. gondii-infected mice were positively correlated, indicating that the observed relationships were highly significant. Therefore, it was concluded that the induction of the immunoproteasomes is a pathogenic mechanism underlying T. gondii infection-induced inflammation.
免疫蛋白酶体是在各种疾病的炎症条件下清除氧化剂损伤蛋白的特定蛋白酶体。刚地弓形虫（Toxoplasma gondii，T. gondii）感染中枢神经系统并引起脑炎。然而，免疫蛋白酶体与弓形虫感染时的脑炎症之间的关系尚未得到充分表征。在本研究中，我们通过腹腔注射建立了体内弓形虫 PLK 株感染小鼠模型，并评估了感染小鼠脑中免疫蛋白酶体亚基的表达。结果表明，首先，感染小鼠脑内的病理变化随时间推移而加重。其次，弓形虫感染后，活化的小胶质细胞和星形胶质细胞经历一系列功能改变和形态转化，包括增殖和迁移。第三，弓形虫感染诱导炎症细胞因子，包括 IFN-γ、IL-1β、TNF-α 和 IL-6 的表达。第四，与 vehicle 处理的脑相比，弓形虫感染小鼠脑中的免疫蛋白酶体亚基低分子量多肽 2（LMP2）、LMP7 和 LMP10 的 mRNA 和蛋白水平通过 RT-qPCR 和 Western blot 分析明显上调，其表达定位于弓形虫感染脑的小胶质细胞、星形胶质细胞和神经元中，通过免疫荧光染色确定。此外，弓形虫感染小鼠脑中免疫蛋白酶体亚基的 Western blot 平均灰度值与阳性小胶质细胞和星形胶质细胞免疫组化信号呈正相关，表明观察到的关系具有高度显著性。因此，结论是免疫蛋白酶体的诱导是弓形虫感染诱导炎症的致病机制。
