IL-1F7b在结核分枝杆菌感染致病过程中的作用机制研究

项目名称： IL-1F7b在结核分枝杆菌感染致病过程中的作用机制研究

项目编号： No.81200003

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学一处

项目作者： 刘海鹏

作者单位： 同济大学

项目金额： 23万元

中文摘要： 结核菌感染及致病过程中重要的免疫调节因子的鉴定和分析对于理解结核病的发病机制、开发新的干预和治疗手段十分重要。IL-1F7b是IL-1家族中重要的抑制性细胞因子，可抑制天然免疫应答。但是，IL-1F7b在结核菌感染过程中的作用还未见报道。我们初步研究发现：（1）IL-1F7b基因的rs6717710 C/T和rs3811047 A/G 2个SNP位点多态性与结核病的发生紧密相关；（2）IL-1F7b能显著抑制巨噬细胞经感染结核菌H37Rv后释放的细胞因子IL-6与TNF-α；（3）IL-1F7b能显著抑制H37Rv诱导的巨噬细胞死亡。以上研究结果提示IL-1F7b可能参与调节结核菌的感染过程，为此，本项目将进一步从分子水平，细胞水平、动物感染模型及临床样本分析等不同层次，研究IL-1F7b在结核菌感染及致病过程中的功能及作用机制，为结核病的预防与治疗提供新的理论基础。

中文关键词： 结核分枝杆菌；IL-37；巨噬细胞；Th1细胞；单核苷酸多态性

英文摘要： Identification and characterization of key immune regulators in the pathogenesis of tuberculosis is essential for the development of anti-TB approaches. IL-1F7b, a member of IL-1 family, is an important anti-inflammatory cytokine as well as a fundamental inhibitor of innate immunity. It exerts both intracellular and extracellular functions. However, the potential functional role of IL-1F7b in the process of Mtb infection remains unknown. Our previous work demonstrated that two SNP sites rs6717710 C/T and rs3811047 A/G are closely associated with the occurrence of tuberculosis. We also observed that IL-1F7b significantly inhibited H37Rv induced production of IL-6 and tumor necorsis factor (TNF) alpha as well as cell death of peritoneal macrophages. These findings suggest that IL-1F7b be an important regulator of Mtb infection. Therefore, here we will explore the functional role of IL-1F7b in the process of Mtb infection of host macrophages and pathogenesis of tuberculosis by combining utilization of macrophage and mouse infection model as well as clinical samples analysis, and clarify the underlying modulation mechanism. This research will finally provide novel molecular target and intervention for the prevention and treatment of tuberculosis.

英文关键词： Mycobacterium tuberculosis；IL-37；macrophage；Th1 cell；single nucleotide polymorphism