cGAS/STING/TBK1/IRF3 Signaling Pathway Activates BMDCs Maturation Following Mycobacterium bovis Infection
cGAS/STING/TBK1/IRF3 Signaling Pathway Activates BMDCs Maturation Following Mycobacterium bovis Infection
复制标题
cGAS/STING/TBK1/IRF3 信号通路在牛分枝杆菌感染后激活 BMDC 成熟
DOI：
10.3390/ijms20040895
复制
发表时间：
2019-02-02
影响因子：
5.6
通讯作者：
Xu, Lihua
中科院分区：
文献类型：
--
作者：
Li, Qiang;Liu, Chunfa;Xu, Lihua
环GMP-AMP合成酶（Cyclic GMP-AMP synthase, cGAS）是一种重要的细胞质DNA传感器，在触发sting依赖信号和诱导I型干扰素（ifn）中起着至关重要的作用。cGAS对细胞内细菌识别和先天免疫应答很重要。然而，cGAS通路在牛分枝杆菌感染过程中对骨髓源性树突状细胞（bmdc）的调节作用尚不清楚。我们假设BMDCs的成熟和激活是由cGAS/STING/TBK1/IRF3信号通路调节的。在本研究中，我们发现牛分枝杆菌通过cGAS信号通路促进BMDCs的表型成熟和功能激活，其中I型IFN及其受体（IFNAR）起作用。此外，我们发现I型IFN通路在牛分枝杆菌感染期间促进CD4+ T细胞与BMDC的增殖。同时，相关细胞因子增加了参与该信号通路的表达。这些数据突出了cGAS和I型IFN通路调控BMDCs成熟和激活的机制，强调了该信号通路和BMDCs对牛分枝杆菌的重要作用。这项研究为cGAS和树突状细胞（DCs）之间的相互作用提供了新的见解，可用于开发新的结核病药物和疫苗。
Cyclic GMP-AMP synthase (cGAS) is an important cytosolic DNA sensor that plays a crucial role in triggering STING-dependent signal and inducing type I interferons (IFNs). cGAS is important for intracellular bacterial recognition and innate immune responses. However, the regulating effect of the cGAS pathway for bone marrow-derived dendritic cells (BMDCs) during Mycobacterium bovis (M. bovis) infection is still unknown. We hypothesized that the maturation and activation of BMDCs were modulated by the cGAS/STING/TBK1/IRF3 signaling pathway. In this study, we found that M. bovis promoted phenotypic maturation and functional activation of BMDCs via the cGAS signaling pathway, with the type I IFN and its receptor (IFNAR) contributing. Additionally, we showed that the type I IFN pathway promoted CD4+ T cells’ proliferation with BMDC during M. bovis infection. Meanwhile, the related cytokines increased the expression involved in this signaling pathway. These data highlight the mechanism of the cGAS and type I IFN pathway in regulating the maturation and activation of BMDCs, emphasizing the important role of this signaling pathway and BMDCs against M. bovis. This study provides new insight into the interaction between cGAS and dendritic cells (DCs), which could be considered in the development of new drugs and vaccines against tuberculosis.