Department of Pathogen Biology and Immunology, Jiangsu Key Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou, Jiangsu Province 221004, China.
Department of Pathogen Biology and Immunology, Jiangsu Key Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou, Jiangsu Province 221004, China.
Acta Trop. 2022 Nov;235:106650. doi: 10.1016/j.actatropica.2022.106650. Epub 2022 Aug 11.
Toxoplasma gondii, an opportunistic pathogenic protozoan, exhibits a strong predilection to infect the brain, causing severe neurological diseases, such as toxoplasmic encephalitis (TE), in immunocompromised patients. Microglia, the resident immune cells in the brain, is reported to play important roles in regulating the neuroinflammation mediated by T. gondii infection. Here we demonstrated that the tachyzoites of T. gondii RH strain could significantly upregulate the expression levels of microglial M1 phenotype markers including IL-1β, IL-6, TNF-α, iNOS and IL18 in activated murine BV2 microglia cells, which were regulated by T. gondii rhoptry protein 18 (TgROP18). Moreover, we found that TgROP18 could enhance the expression of M1 phenotype markers in activated murine BV2 microglia cells via activating NF-κB signal pathway. Additionally, TgROP18 was suggested to interact with the host p65 in activated murine BV2 microglia cells and induce the phosphorylation of p65 at S536. In summary, the present study demonstrated that TgROP18 could promote the activated microglia to polarize to M1 phenotype and enhanced the expression of pro-inflammatory factors via activating NF-κB signal pathway, which could contribute to elucidating the mechanism underlying the neuroinflammation mediated by activated microglia in the brain with T. gondii infection.
刚地弓形虫是一种机会致病的原生动物，它强烈倾向于感染大脑，导致免疫功能低下的患者发生严重的神经疾病，如弓形虫脑炎（TE）。据报道，小胶质细胞是大脑中的固有免疫细胞，在调节弓形虫感染介导的神经炎症中发挥重要作用。在这里，我们证明了 RH 株的速殖子可以显著上调激活的小鼠 BV2 小胶质细胞中 M1 表型标志物的表达水平，包括 IL-1β、IL-6、TNF-α、iNOS 和 IL18，这是由弓形虫 rhoptry 蛋白 18（TgROP18）调节的。此外，我们发现 TgROP18 可以通过激活 NF-κB 信号通路来增强激活的小鼠 BV2 小胶质细胞中 M1 表型标志物的表达。此外，TgROP18 被认为可以与激活的小鼠 BV2 小胶质细胞中的宿主 p65 相互作用，并诱导 p65 在 S536 处磷酸化。总之，本研究表明，TgROP18 可以通过激活 NF-κB 信号通路促进激活的小胶质细胞向 M1 表型极化，并增强促炎因子的表达，这有助于阐明弓形虫感染大脑中激活的小胶质细胞介导的神经炎症的机制。
