School of Life Science and Engineering, Foshan University, Foshan, 528000, China.
College of Biology Engineering and Food, Henan University of Animal Husbandry and Economy, Zhengzhou, 450046, China.
Dev Comp Immunol. 2022 Feb;127:104296. doi: 10.1016/j.dci.2021.104296. Epub 2021 Oct 14.
Stimulator of interferon gene (STING), an adaptor molecule in the immune system, is involved in mediating the response to viral and bacterial infections, anti-tumor immunity, autoimmune diseases, and lipid metabolism. There have been reports on the cloning and function of STING in humans, pigs, chickens, and cats; however, STING has not been characterized in non-human primates or monkeys to date. Therefore, in this study, the rhesus macaque (Macaca mulata) STING gene was cloned, and we performed preliminary functional tests to examine its role in the interferon (IFN) pathway. The M. mulatta STING complementary DNA was 1140 bp in length and encoded 380 amino acid residues. Phylogenetic analysis showed that Homo sapiens and M. mulatta STING are closely related and clustered on the same branch. M. mulatta STING was confirmed to increase the promoter activities of IFN-β, nuclear factor-κB, and interferon-sensitive response element, and STING overexpression increased the mRNA levels of IFN-α, IFN-β, and interferon regulatory factor 3. Infection of Marc-145 cells with porcine reproductive and respiratory syndrome virus activated STING, and its expression increased along with increases in viral multiplicity of infection titer and time. Moreover, STING expression was time- and dose-dependently up-regulated by poly (I:C) and poly (dA:dT) treatments in Marc-145 cells. In summary, these results highlight STING as a vital immune system signal protein in the IFN pathway. This study provides a basis for understanding the immune characteristics of M. mulatta, and may have important implications for both monkey and human diseases.
干扰素基因刺激物（STING）是免疫系统中的一种衔接分子，参与介导对病毒和细菌感染、抗肿瘤免疫、自身免疫性疾病和脂质代谢的反应。已经有关于人类、猪、鸡和猫中 STING 的克隆和功能的报道；然而，迄今为止，非人类灵长类动物或猴子中的 STING 尚未得到表征。因此，在本研究中，我们克隆了恒河猴（Macaca mulatta）的 STING 基因，并进行了初步的功能测试，以研究其在干扰素（IFN）途径中的作用。M. mulatta STING cDNA 长 1140bp，编码 380 个氨基酸残基。系统发育分析表明，智人和恒河猴 STING 密切相关，并聚类在同一分支上。恒河猴 STING 被证实可增加 IFN-β、核因子-κB 和干扰素敏感反应元件的启动子活性，并且 STING 过表达可增加 IFN-α、IFN-β 和干扰素调节因子 3 的 mRNA 水平。Marc-145 细胞感染猪繁殖与呼吸综合征病毒可激活 STING，其表达随病毒感染复数滴度和时间的增加而增加。此外，多聚（I:C）和多聚（dA:dT）处理可时间和剂量依赖性地上调 Marc-145 细胞中的 STING 表达。总之，这些结果强调了 STING 作为 IFN 途径中重要的免疫系统信号蛋白的作用。本研究为了解恒河猴的免疫特征提供了基础，可能对猴子和人类疾病都具有重要意义。
