Department of Marine Life Sciences, Jeju National University, Jeju 63243, Republic of Korea.
Marine Science Institute, Jeju National University, Jeju 63333, Republic of Korea.
Biomolecules. 2023 Feb 8;13(2):324. doi: 10.3390/biom13020324.
Stimulator of interferon genes (STING) is an adapter protein that is activated when cyclic dinucleotides (CDNs) are present. CDNs originate from the cytosolic DNA of both pathogens and hosts. STING activation promotes efficient immune responses against viral infections; however, its impact in bacterial infections is unclear. In this study, we investigated the role of Sting in bacterial infections by successfully creating a -deficient ( with a 4-bp deletion) knockout zebrafish model using CRISPR/Cas9. The transcriptional modulation of genes downstream of cGAS (cyclic GMP-AMP synthase)-Sting pathway-related genes was analyzed in seven-day-old wild-type (WT) and embryos, as well as in four-day-old LPS-stimulated embryos. The expression of downstream genes was higher in than in healthy WT fish. The late response was observed in larvae following LPS treatment, demonstrating the importance of Sting-induced immunity during bacterial infection by activating the cGAS-STING pathway. Furthermore, adult fish had a high mortality rate and significantly downregulated cGAS-STING pathway-related genes during () infection. In addition, we assessed NF-κB pathway genes following infection. Our results show fluctuating patterns of ( and ( expression, which is likely due to the influence of other NF-κB pathway-related immune genes. In summary, this study demonstrates the important role of Sting against bacterial infection.
干扰素基因刺激物 (STING) 是一种衔接蛋白，当环二核苷酸 (CDN) 存在时被激活。CDN 来源于病原体和宿主的胞质 DNA。STING 的激活促进了对病毒感染的有效免疫反应；然而，其在细菌感染中的作用尚不清楚。在这项研究中，我们通过使用 CRISPR/Cas9 成功地创建了一个 Sting 缺陷型（带有 4 个碱基对缺失）的斑马鱼模型，以研究 Sting 在细菌感染中的作用。在 7 天大的野生型 (WT) 和 胚胎以及 4 天大的 LPS 刺激的胚胎中分析了 cGAS（环鸟苷酸-腺苷酸合酶）-Sting 通路相关基因下游的基因转录调节。下游基因的表达在 中高于健康的 WT 鱼。在 LPS 处理后， 幼虫出现晚期反应，表明通过激活 cGAS-STING 通路， Sting 诱导的免疫在细菌感染中很重要。此外，在 感染期间，成年 鱼的死亡率很高，并且 cGAS-STING 通路相关基因的表达显著下调。此外，我们还评估了 NF-κB 通路基因在 感染后的表达情况。我们的结果显示，在 感染后， ( 和 ( 的表达呈波动模式，这可能是由于其他 NF-κB 通路相关免疫基因的影响。总之，这项研究表明了 Sting 对抗细菌感染的重要作用。
