Key Laboratory of Zoonosis Research, Ministry of Education; College of Veterinary Medicine, Jilin University, 5333 Xian Road, Changchun, 130062, China.
Jilin Agricultural Science and Technology University, Jilin, China.
Parasitol Res. 2020 Mar;119(3):1023-1033. doi: 10.1007/s00436-019-06588-0. Epub 2020 Feb 17.
Toxoplasma gondii is an important zoonotic protozoan worldwide which infects most of warm-blooded mammals and birds, including human, and cause toxoplasmosis. As an intracellular parasite, T. gondii must evade host immune surveillance, such as IL-12 and IFN-γ, in order to survive and multiply in macrophages and other host cells. By delaying IL-12 secretion of host macrophages within 24 h after infection, T. gondii ensures not only self-survival but also the establishment of chronic infection of host cells. MicroRNA plays an important role in regulating gene transcription and translation. The mechanisms of IL-12 production during T. gondii infection are still unknown. Thus, understanding how the parasites manipulate IL-12 production by host macrophage is critical for the effective prevention and therapy of T. gondii infection. In the present study, regulation of delayed macrophage IL-12 production during T. gondii infection was explored. We found that the production of IL-12 after T. gondii infection was inhibited during the first 24 h and then resumed. The expression pattern of miR-187 production was consistent with the production pattern of IL-12 during T. gondii infection. The downregulation of miR-187 promoted Akt and P65 phosphorylation and delayed IL-12 production at late stage (after 24 h) of T. gondii infection. Dual-luciferase reporter assay indicated that MiR-187 targeted the NFKBIZ gene. Our results suggested that the delayed IL-12 production in mouse macrophages during T. gondii infection was regulated by miR-187.
刚地弓形虫是一种重要的世界性动物源性原虫，感染大多数温血哺乳动物和鸟类，包括人类，并引起弓形体病。作为一种细胞内寄生虫，刚地弓形虫必须逃避宿主的免疫监视，如 IL-12 和 IFN-γ，以在巨噬细胞和其他宿主细胞中存活和繁殖。刚地弓形虫在感染后 24 小时内延迟宿主巨噬细胞中 IL-12 的分泌，不仅确保了自身的存活，而且还建立了宿主细胞的慢性感染。MicroRNA 在调节基因转录和翻译中起着重要作用。在刚地弓形虫感染期间，IL-12 产生的机制尚不清楚。因此，了解寄生虫如何操纵宿主巨噬细胞中 IL-12 的产生对于刚地弓形虫感染的有效预防和治疗至关重要。本研究探讨了刚地弓形虫感染期间延迟巨噬细胞 IL-12 产生的调控机制。我们发现，刚地弓形虫感染后 24 小时内 IL-12 的产生受到抑制，然后恢复。miR-187 的表达模式与刚地弓形虫感染期间 IL-12 的产生模式一致。miR-187 的下调促进了 Akt 和 P65 的磷酸化，并延迟了刚地弓形虫感染后期（24 小时后）IL-12 的产生。双荧光素酶报告基因实验表明，miR-187 靶向 NFKBIZ 基因。我们的结果表明，刚地弓形虫感染小鼠巨噬细胞中 IL-12 的延迟产生受 miR-187 调节。
