College of Agriculture, Ningxia University, Xixia District, Yinchuan 750021, China.
State Key Lab of Agrobiotechnology, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
Int J Mol Sci. 2019 Feb 19;20(4):895. doi: 10.3390/ijms20040895.
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 () 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 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 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 . 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.
环鸟苷酸-腺苷酸合成酶 (cGAS) 是一种重要的细胞质 DNA 传感器，在触发 STING 依赖性信号和诱导 I 型干扰素 (IFNs) 中发挥关键作用。cGAS 对于细胞内细菌识别和先天免疫反应至关重要。然而，cGAS 途径在 () 感染期间对骨髓来源的树突状细胞 (BMDC) 的调节作用尚不清楚。我们假设 cGAS/STING/TBK1/IRF3 信号通路调节 BMDC 的成熟和激活。在这项研究中，我们发现 通过 cGAS 信号通路促进 BMDC 的表型成熟和功能激活，I 型 IFN 及其受体 (IFNAR) 发挥作用。此外，我们表明 I 型 IFN 途径通过感染促进 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。这些数据强调了 cGAS 和 I 型 IFN 途径在调节 BMDC 成熟和激活中的机制，强调了该信号通路和 BMDCs 对 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，这可能有助于开发针对结核病的新药和疫苗。
