自噬和Toll样受体（TLRs）介导的炎症反应都是抗MTB的天然防御机制，二者存在相互作用。本项目前期研究结合文献报道证实miR-20a/miR-17既可结合TLRs信号的负调控因子SIRPa，调控炎症反应，又可结合多个自噬相关基因（ATGs），调控自噬。本项目进一步提出SIRPa和ATGs可竞争性结合miR-20a/miR-17从而构成ceRNAs网络，炎症反应和自噬可通过此ceRNA网络互相调控。拟开展：1）构建自噬、炎症和MTB感染等巨噬细胞模型，利用小RNA高通量测序技术筛选共同差异表达miRNAs；2）利用荧光素酶报告法等技术明确miR-20a/miR-17对SIRPa和ATGs的靶向关系，确证miR-20a/miR-17相关ceRNAs网络的存在。3）通过RNAi、免疫荧光和透射电镜等技术揭示miR-20a/miR-17相关ceRNAs网络调控抗MTB炎症反应和自噬的作用机制。

Autophagy and toll like receptors (TLRs) mediated inflammatory responses are natural defense mechanisms against Mycobacterium tuberculosis (MTB), and they are closely tied and regulated eath other. In our and other study, miR-20a and miR-17 can combine with a negative regulator of TLRs signal (SIRPa) and multiple autophagy related genes (ATGs), then regulate inflammatory response and autophagy. We further speculate that inflammatory responses and autophagy can regulate each other by ceRNAs network that miR-20a/miR-17 competitively bind miR-20a/miR-17. The following studies will be carried out. 1) Severl macrophage models of autophagy, inflammation and MTB infection are construted, and miRNAs with collective differential expression are screened out by small RNA high-throughput sequencing technology. 2) To clarify the targeting relationship between miR-20a/miR-17 and SIRPa or ATGs and confirm the existence of miR-20a/miR-17 related ceRNAs network by using qPCR, western bolt and luciferase reporter assay etc. 3) Reveal the mechanism of miR-20a/miR-17 related ceRNAs network in regulating the inflammatory response and autophagy against MTB in macrophages by using RNAi, immunofluorescence and transmission electron microscopy etc.