College of Veterinary Medicine, Shandong Agricultural University, Tai'an, 271018, Shandong, China.
College of Veterinary Medicine, Hebei Agricultural University, Baoding, 071001, Hebei, China.
Vet Res. 2022 Feb 5;53(1):10. doi: 10.1186/s13567-022-01027-y.
Cell death and inflammation are intimately linked during mastitis due to Staphylococcus aureus (S. aureus). Pyroptosis, a programmed necrosis triggered by gasdermin protein family, often occurs after inflammatory caspase activation. Many pathogens invade host cells and activate cell-intrinsic death mechanisms, including pyroptosis, apoptosis, and necroptosis. We reported that bovine mammary epithelial cells (MAC-T) respond to S. aureus by NOD-like receptor protein 3 (NLRP3) inflammasome activation through K efflux, leading to the recruitment of apoptosis-associated speck-like protein (ASC) and the activation of caspase-1. The activated caspase-1 cleaves gasdermin D (GSDMD) and forms a N-terminal pore forming domain that drives swelling and membrane rupture. Membrane rupture results in the release of the pro-inflammatory cytokines IL-18 and IL-1β, which are activated by caspase-1. Can modulate GSDMD activation by NLRP3-dependent caspase-1 activation and then cause pyroptosis of bovine mammary epithelial cells.
金黄色葡萄球菌（S. aureus）性乳腺炎中细胞死亡和炎症密切相关。焦亡是一种由gasdermin 蛋白家族触发的程序性细胞坏死，通常发生在炎症性半胱天冬酶激活之后。许多病原体入侵宿主细胞并激活细胞内固有死亡机制，包括焦亡、细胞凋亡和坏死性凋亡。我们报道，牛乳腺上皮细胞（MAC-T）通过钾离子外流对金黄色葡萄球菌作出反应，通过 NOD 样受体蛋白 3（NLRP3）炎性小体激活，导致凋亡相关斑点样蛋白（ASC）的募集和半胱天冬酶-1 的激活。激活的半胱天冬酶-1 切割 gasdermin D（GSDMD）并形成一个 N 端孔形成结构域，导致肿胀和膜破裂。膜破裂导致促炎细胞因子 IL-18 和 IL-1β的释放，这些细胞因子被半胱天冬酶-1 激活。可通过 NLRP3 依赖性半胱天冬酶-1 激活调节 GSDMD 激活，然后导致牛乳腺上皮细胞发生焦亡。
