Liu Kangjun, Zhou Xi, Fang Li, Dong Junsheng, Cui Luying, Li Jun, Meng Xia, Zhu Guoqiang, Li Jianji, Wang Heng
College of Veterinary Medicine, Yangzhou University, Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu 225009, China; Joint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou, Jiangsu 225009, China; Joint International Research Laboratory of Important Animal Infectious Diseases and Zoonoses of Jiangsu Higher Education Institutions, Yangzhou, Jiangsu 225009, China.
Int Immunopharmacol. 2022 Nov;112:109200. doi: 10.1016/j.intimp.2022.109200. Epub 2022 Sep 2.
Staphylococcus aureus (S. aureus) is known to induce chronic and persistent bovine mammary infection, which affects milk quality and leads to premature culling. The ability of S. aureus to invade mammalian cells protects it from clearance by the immune system. Mitophagy is important in cell homeostasis, and can be utilized by pathogens for immune escape. However, mitophagy's role in S. aureus-associated bovine mastitis remains unclear. Here, S. aureus infection induced mitophagy and enhanced mitochondrial translocation of parkin in MAC-T cells. After mitophagy inhibition by Mdivi-1 treatment or PTEN-induced putative kinase 1 (PINK1) silencing in MAC-T cells infected with S. aureus, NOD-like receptor protein 3 (NLRP3) inflammasome activation and p65 and IκBα phosphorylation were increased. Meanwhile, PINK1 overexpression had the opposite effects. In addition, NLRP3 inflammasome overactivation and enhanced p65 and IκBα phosphorylation caused by PINK1 silencing were reversed by MitoTEMPO. Furthermore, PINK1/parkin-mediated mitophagy promoted S. aureus survival and contributed to persistent S. aureus infection. These findings provide new insights into S. aureus invasion in bovine mastitis.
金黄色葡萄球菌（S. aureus）已知会引发慢性持续性牛乳腺炎感染，这种感染会影响牛奶质量并导致奶牛过早被淘汰。金黄色葡萄球菌侵入哺乳动物细胞的能力使其免受免疫系统的清除。线粒体自噬在细胞内稳态中起重要作用，病原体可利用它来实现免疫逃逸。然而，线粒体自噬在与金黄色葡萄球菌相关的牛乳腺炎中的作用仍不清楚。在此，金黄色葡萄球菌感染诱导了MAC-T细胞中的线粒体自噬，并增强了帕金蛋白的线粒体转位。在用Mdivi-1处理或在感染金黄色葡萄球菌的MAC-T细胞中沉默PTEN诱导的假定激酶1（PINK1）来抑制线粒体自噬后，NOD样受体蛋白3（NLRP3）炎性小体激活以及p65和IκBα磷酸化增加。同时，PINK1过表达则产生相反的效果。此外，MitoTEMPO可逆转由PINK1沉默引起的NLRP3炎性小体过度激活以及p65和IκBα磷酸化增强。此外，PINK1/帕金介导的线粒体自噬促进了金黄色葡萄球菌的存活，并导致金黄色葡萄球菌持续感染。这些发现为金黄色葡萄球菌在牛乳腺炎中的侵袭提供了新的见解。
