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.
Keywords: Akt; IL-12; NF-κB; T. gondii; miRNAs.