Frontiers in Immunology (Oct 2022)
Porcine cGAS-STING signaling induced autophagy inhibits STING downstream IFN and apoptosis
- Nengwen Xia,
- Nengwen Xia,
- Nengwen Xia,
- Nengwen Xia,
- Wanglong Zheng,
- Wanglong Zheng,
- Wanglong Zheng,
- Wanglong Zheng,
- Sen Jiang,
- Sen Jiang,
- Sen Jiang,
- Sen Jiang,
- Qi Cao,
- Qi Cao,
- Qi Cao,
- Qi Cao,
- Jia Luo,
- Jia Luo,
- Jia Luo,
- Jia Luo,
- Jiajia Zhang,
- Jiajia Zhang,
- Jiajia Zhang,
- Jiajia Zhang,
- Yulin Xu,
- Yulin Xu,
- Yulin Xu,
- Yulin Xu,
- Shaohua Sun,
- Shaohua Sun,
- Shaohua Sun,
- Shaohua Sun,
- Kaili Zhang,
- Kaili Zhang,
- Kaili Zhang,
- Kaili Zhang,
- Nanhua Chen,
- Nanhua Chen,
- Nanhua Chen,
- Nanhua Chen,
- François Meurens,
- François Meurens,
- Jianzhong Zhu,
- Jianzhong Zhu,
- Jianzhong Zhu,
- Jianzhong Zhu
Affiliations
- Nengwen Xia
- Comparative Medicine Research Institute, Yangzhou University, Yangzhou, China
- Nengwen Xia
- College of Veterinary Medicine, Yangzhou University, Yangzhou, China
- Nengwen Xia
- Joint International Research Laboratory of Agriculture and Agri-Product Safety, Yangzhou, China
- Nengwen Xia
- Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, China
- Wanglong Zheng
- Comparative Medicine Research Institute, Yangzhou University, Yangzhou, China
- Wanglong Zheng
- College of Veterinary Medicine, Yangzhou University, Yangzhou, China
- Wanglong Zheng
- Joint International Research Laboratory of Agriculture and Agri-Product Safety, Yangzhou, China
- Wanglong Zheng
- Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, China
- Sen Jiang
- Comparative Medicine Research Institute, Yangzhou University, Yangzhou, China
- Sen Jiang
- College of Veterinary Medicine, Yangzhou University, Yangzhou, China
- Sen Jiang
- Joint International Research Laboratory of Agriculture and Agri-Product Safety, Yangzhou, China
- Sen Jiang
- Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, China
- Qi Cao
- Comparative Medicine Research Institute, Yangzhou University, Yangzhou, China
- Qi Cao
- College of Veterinary Medicine, Yangzhou University, Yangzhou, China
- Qi Cao
- Joint International Research Laboratory of Agriculture and Agri-Product Safety, Yangzhou, China
- Qi Cao
- Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, China
- Jia Luo
- Comparative Medicine Research Institute, Yangzhou University, Yangzhou, China
- Jia Luo
- College of Veterinary Medicine, Yangzhou University, Yangzhou, China
- Jia Luo
- Joint International Research Laboratory of Agriculture and Agri-Product Safety, Yangzhou, China
- Jia Luo
- Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, China
- Jiajia Zhang
- Comparative Medicine Research Institute, Yangzhou University, Yangzhou, China
- Jiajia Zhang
- College of Veterinary Medicine, Yangzhou University, Yangzhou, China
- Jiajia Zhang
- Joint International Research Laboratory of Agriculture and Agri-Product Safety, Yangzhou, China
- Jiajia Zhang
- Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, China
- Yulin Xu
- Comparative Medicine Research Institute, Yangzhou University, Yangzhou, China
- Yulin Xu
- College of Veterinary Medicine, Yangzhou University, Yangzhou, China
- Yulin Xu
- Joint International Research Laboratory of Agriculture and Agri-Product Safety, Yangzhou, China
- Yulin Xu
- Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, China
- Shaohua Sun
- Comparative Medicine Research Institute, Yangzhou University, Yangzhou, China
- Shaohua Sun
- College of Veterinary Medicine, Yangzhou University, Yangzhou, China
- Shaohua Sun
- Joint International Research Laboratory of Agriculture and Agri-Product Safety, Yangzhou, China
- Shaohua Sun
- Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, China
- Kaili Zhang
- Comparative Medicine Research Institute, Yangzhou University, Yangzhou, China
- Kaili Zhang
- College of Veterinary Medicine, Yangzhou University, Yangzhou, China
- Kaili Zhang
- Joint International Research Laboratory of Agriculture and Agri-Product Safety, Yangzhou, China
- Kaili Zhang
- Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, China
- Nanhua Chen
- Comparative Medicine Research Institute, Yangzhou University, Yangzhou, China
- Nanhua Chen
- College of Veterinary Medicine, Yangzhou University, Yangzhou, China
- Nanhua Chen
- Joint International Research Laboratory of Agriculture and Agri-Product Safety, Yangzhou, China
- Nanhua Chen
- Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, China
- François Meurens
- Unit of Biology, Epidemiology and Risk Analysis in Animal Health (BIOEPAR), French National Institute for Agriculture, Food, and Environment (INRAE), Oniris, Nantes, France
- François Meurens
- Department of Veterinary Microbiology and Immunology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, Canada
- Jianzhong Zhu
- Comparative Medicine Research Institute, Yangzhou University, Yangzhou, China
- Jianzhong Zhu
- College of Veterinary Medicine, Yangzhou University, Yangzhou, China
- Jianzhong Zhu
- Joint International Research Laboratory of Agriculture and Agri-Product Safety, Yangzhou, China
- Jianzhong Zhu
- Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, China
- DOI
- https://doi.org/10.3389/fimmu.2022.1021384
- Journal volume & issue
-
Vol. 13
Abstract
The innate immune DNA sensing cGAS-STING signaling pathway has been widely recognized for inducing interferons (IFNs) and subsequent antiviral state. In addition to IFN, the cGAS-STING pathway also elicits other cell autonomous immunity events including autophagy and apoptosis. However, the downstream signaling events of this DNA sensing pathway in livestock have not been well defined. Here, we systematically analyzed the porcine STING (pSTING) induced IFN, autophagy and apoptosis, revealed the distinct dynamics of three STING downstream events, and established the IFN independent inductions of autophagy and apoptosis. Further, we investigated the regulation of autophagy on pSTING induced IFN and apoptosis. Following TBK1-IRF3-IFN activation, STING induced Atg5/Atg16L1 dependent autophagy through LIR motifs. In turn, the autophagy likely promoted the pSTING degradation, inhibited both IFN production and apoptosis, and thus restored the cell homeostasis. Therefore, this study sheds lights on the molecular mechanisms of innate immunity in pigs.
Keywords