弓形虫对DNA受体天然免疫通路的激活及机制研究-病原生物学专业论文.docx

暨南大学 暨南大学 2014 届硕士研究生学位论文 PAGE PAGE IV 结论： 1. 弓形虫 DNA 能够激活 IRF3，使其二聚化，诱导 IFN-β 的产生，进而促 进 ISRE 的表达，该激活途径有可能通过 cGAS-STING 信号通路。 2. 弓形虫速殖子可以促进 NF-κB 启动子表达，活化 NF-κB 信号通路。 3. 弓形虫速殖子可以抑制 IL-6、IL-18、ISG15、STING 的 mRNA 转录。TBK1 基因在弓形虫速殖子对 IL-18、ISG15 mRNA 转录的抑制作用中起着一定的作用； 弓形虫依赖于 TBK1 基因从而抑制 IL-6 mRNA 的转录。 关键字：弓形虫；天然免疫；cGAS；Sting；IFN-β；TBK1；IRF3； Abstract Objective: Toxoplasma gondii can infect almost all of the nucleated cells, about a third of the worlds population have ever been infected with Toxoplasma. Toxoplasma can infect the host cells and form the parasitophorous vacuole in host cell. On the one hand，Toxoplasma regulated the expression and secretion of immunomodulatory cytokines; on the other hand , the growth of T. gondii in vacuoles interfering the signal transduction of host cell, thereby inhibiting the host cell response against Toxoplasma gondii infection. In the process of organism infections or tissue damage, exogenous DNA accumulated in the cytoplasm or their own DNA can trigger a strong immune response, inducing product a series of cytokines, such as IFN - beta. Identification of exogenous DNA by receptor DNA is a key link in the process of the body against bacteria and viruses. Studies have reported that the worm cavity of Toxoplasma can be broken under the action of IFN - gamma, after a series of immune reaction Toxoplasma removal by the body, at the same time toxoplasma DNA can be detected in the cytoplasm. Based on the above research background, this experiment was to study after the bubble bursting, the toxoplasma DNA got into the host cytoplasm could be recognized by DNA receptor and activation downstream signaling pathways, induced the type I interferon and whether activation of the pathway dependent on the STING, cGAS and TBK1 key genes, thus showing innate immune mechanism of toxoplasma infection, to understand the intracellular pathogens innate immune mechanism provides new content. Methods: Using human foreskin fibroblasts (HFF) to cu