Staphylococcus pseudintermedius induces pyroptosis of canine corneal epithelial cells by activating the ROS-NLRP3 signalling pathway
文献类型: 外文期刊
作者: Wang, Zhihao 1 ; Guo, Long 1 ; Yuan, Changning 1 ; Zhu, Chengcheng 1 ; Li, Jun 1 ; Zhong, Haoran 4 ; Mao, Peng 1 ; Li, Jianji 1 ; Cui, Luying 1 ; Dong, Junsheng 1 ; Liu, Kangjun 1 ; Meng, Xia 1 ; Zhu, Guoqiang 1 ; Wang, Heng 1 ;
作者机构: 1.Yangzhou Univ, Coll Vet Med, Jiangsu Coinnovat Ctr Prevent & Control Important, Yangzhou, Jiangsu, Peoples R China
2.Yangzhou Univ, Int Res Lab Prevent & Control Important Anim Infec, Yangzhou, Peoples R China
3.Minist Educ, Joint Int Res Lab Agr & Agriprod Safety, Yangzhou, Jiangsu, Peoples R China
4.Chinese Acad Agr Sci, Shanghai Vet Res Inst, Natl Reference Lab Anim Schistosomiasis, Shanghai, Peoples R China
关键词: Staphylococcus pseudintermedius; canine corneal epithelial cells; intracellular infection; pyroptosis; NLRP3 inflammasome; reactive oxygen species
期刊名称:VIRULENCE ( 影响因子:5.2; 五年影响因子:5.9 )
ISSN: 2150-5594
年卷期: 2024 年 15 卷 1 期
页码:
收录情况: SCI
摘要: Staphylococcus pseudintermedius (S. pseudintermedius) is a common pathogen that causes canine corneal ulcers. However, the pathogenesis remained unclear. In this study, it has been demonstrated that S. pseudintermedius invaded canine corneal epithelial cells (CCECs) intracellularly, mediating oxidative damage and pyroptosis by promoting the accumulation of intracellular reactive oxygen species (ROS) and activating the NLRP3 inflammasome. The canine corneal stroma was infected with S. pseudintermedius to establish the canine corneal ulcer model in vivo. The intracellular infectious model in CCECs was established in vitro to explore the mechanism of the ROS - NLRP3 signalling pathway during the S. pseudintermedius infection by adding NAC or MCC950. Results showed that the expression of NLRP3 and gasdermin D (GSDMD) proteins increased significantly in the infected corneas (p < 0.01). The intracellular infection of S. pseudintermedius was confirmed by transmission electron microscopy and immunofluorescent 3D imaging. Flow cytometry analysis revealed that ROS and pyroptosis rates increased in the experimental group in contrast to the control group (p < 0.01). Furthermore, NAC or MCC950 inhibited activation of the ROS - NLRP3 signalling pathway and pyroptosis rate significantly, by suppressing pro-IL-1 beta, cleaved-IL-1 beta, pro-caspase-1, cleaved-caspase-1, NLRP3, GSDMD, GSDMD-N, and HMGB1 proteins. Thus, the research confirmed that oxidative damage and pyroptosis were involved in the process of CCECs infected with S. pseudintermedius intracellularly by the ROS - NLRP3 signalling pathway. The results enrich the understanding of the mechanisms of canine corneal ulcers and facilitate the development of new medicines and prevention measures.
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