Song Yinjuan, Dong Yuhui, Liao Yi, Liang Zhengmin, Yao Jiao, Zhou Xiangmei
Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China; College of Animal & Veterinary Science, Southwest Minzu University, Chengdu, Sichuan 610041, China.
J Infect. 2021 Jul;83(1):61-68. doi: 10.1016/j.jinf.2021.04.014. Epub 2021 Apr 20.
Caspases are classified as inflammatory or apoptotic category. Inflammatory caspases participate in inflammasome activation, while apoptotic caspases mediate apoptotic activation. Previous studies have shown that apoptotic caspases prevent the production of IFN-β during apoptosis or virus infection. However, the relationship between apoptotic caspases and IFN-β production during intracellular bacterial infection is still unclear. Here, we investigated the role of apoptotic caspases in IFN-β production induced by Mycobacterium bovis (M. bovis) infection. M. bovis is an intracellular bacterium and belongs to the Mycobacterium tuberculosis complex. M. bovis infection can cause tuberculosis in animals and human beings. In the current study, we found that M. bovis infection triggered mitochondrial stress, which caused the leakage of cytochrome c into the cytoplasm, and in turn, activated the downstream caspase-9 and-3. Furthermore, our results showed that activation of apoptotic caspases reduced IFN-β production during M. bovis infection and vice versa. Confocal microscopy analysis revealed that apoptotic caspases prevented IFN-β production by decreasing p-IRF3 nuclear translocation. Our findings demonstrate that apoptotic caspases negatively regulate the production of IFN-β induced by an intracellular bacterial infection.
半胱天冬酶分为炎性或凋亡性类别。炎性半胱天冬酶参与炎性小体激活，而凋亡性半胱天冬酶介导凋亡激活。先前的研究表明，凋亡性半胱天冬酶在细胞凋亡或病毒感染期间可阻止IFN-β的产生。然而，在细胞内细菌感染期间凋亡性半胱天冬酶与IFN-β产生之间的关系仍不清楚。在此，我们研究了凋亡性半胱天冬酶在牛分枝杆菌（M. bovis）感染诱导的IFN-β产生中的作用。牛分枝杆菌是一种细胞内细菌，属于结核分枝杆菌复合群。牛分枝杆菌感染可导致动物和人类患结核病。在当前研究中，我们发现牛分枝杆菌感染引发线粒体应激，导致细胞色素c泄漏到细胞质中，进而激活下游的半胱天冬酶-9和-3。此外，我们的结果表明，凋亡性半胱天冬酶的激活在牛分枝杆菌感染期间降低了IFN-β的产生，反之亦然。共聚焦显微镜分析显示，凋亡性半胱天冬酶通过减少p-IRF3核转位来阻止IFN-β的产生。我们的研究结果表明，凋亡性半胱天冬酶对细胞内细菌感染诱导的IFN-β产生具有负调控作用。
