Zhou Yang, Zhao Shasha, Gao Xiao, Jiang Songhong, Ma Jialu, Wang Rui, Li Qing, Qin Leiying, Tong Zhizi, Wu Junwei, Zhao Jianjun
College of Veterinary Medicine, Southwest University, Chongqing 402460, China.
Immunology Research Center, Medical Research Institute, Southwest University, Chongqing 402460, China.
Pathogens. 2021 Mar 4;10(3):300. doi: 10.3390/pathogens10030300.
Type I interferon (IFN) induction is a critical component of innate immune response to viral and bacterial infection, including , but whether it activates the signaling in macrophages and the regulation mechanisms is less well understood. Here we show that infection promoted the IFN-β mRNA expression and stimulator of IFN genes (STING)/TANK-binding kinase 1 (TBK1)/interferon regulatory factor 3 (IRF3)-dependent production of IFN-β. Infection with induced caspase recruitment domain and membrane-associated guanylate kinase-like domain protein 3 (CARMA3) expression at both the mRNA and protein levels. The heat-killed bacteria failed to trigger IRF3 phosphorylation and upregulation of CARMA3 expression. However, overexpression of CARMA3 did not affect phosphorylation of TBK1 or IRF3 in RAW264.7 cells, J774A.1 macrophages, and mouse embryonic fibroblast (MEF) cells. In conclusion, infection induces STING/TBK1/IRF3-mediated IFN-β production in a CARMA3-independent manner.
I型干扰素（IFN）的诱导是对病毒和细菌感染的固有免疫反应的关键组成部分，包括但对其是否激活巨噬细胞中的信号传导以及调节机制了解较少。在这里，我们表明感染促进了IFN-β mRNA表达以及干扰素基因刺激因子（STING）/ Tank结合激酶1（TBK1）/干扰素调节因子3（IRF3）依赖性的IFN-β产生。感染诱导了半胱天冬酶募集结构域和膜相关鸟苷酸激酶样结构域蛋白3（CARMA3）在mRNA和蛋白质水平上的表达。热灭活的细菌未能触发IRF3磷酸化和CARMA3表达上调。然而，CARMA3的过表达在RAW264.7细胞、J774A.1巨噬细胞和小鼠胚胎成纤维细胞（MEF）中不影响TBK1或IRF3的磷酸化。总之，感染以不依赖CARMA3的方式诱导STING/TBK1/IRF3介导的IFN-β产生。
