Staphylococcus aureus , a versatile Gram‐positive bacterium, is the main cause of bone and joint infections (BJI), which are prone to recurrence. The inflammasome is an immune signaling platform that assembles after pathogen recognition. It activates proteases, most notably caspase‐1 that proteolytically matures and promotes the secretion of mature IL‐1β and IL‐18. The role of inflammasomes and caspase‐1 in the secretion of mature IL‐1β and in the defence of S. aureus ‐infected osteoblasts has not yet been fully investigated. We show here that S. aureus ‐infected osteoblast‐like MG‐63 but not caspase‐1 knock‐out CASP1 ^−/− MG‐63 cells, which were generated using CRISPR‐Cas9 technology, activate the inflammasome as monitored by the release of mature IL‐1β. The effect was strain‐dependent. The use of S. aureus deletion and complemented phenole soluble modulins (PSMs) mutants demonstrated a key role of PSMs in inflammasomes‐related IL‐1β production. Furthermore, we found that the lack of caspase‐1 in CASP1 ^−/− MG‐63 cells impairs their defense functions, as bacterial clearance was drastically decreased in CASP1 ^−/− MG‐63 compared to wild‐type cells. Our results demonstrate that osteoblast‐like MG‐63 cells play an important role in the immune response against S. aureus infection through inflammasomes activation and establish a crucial role of caspase‐1 in bacterial clearance.

中文翻译：

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caspase-1 参与金黄色葡萄球菌感染的成骨细胞样 MG-63 细胞中炎症小体的激活和细菌清除。


金黄色葡萄球菌是一种多功能革兰氏阳性细菌，是骨和关节感染 (BJI) 的主要原因，且容易复发。炎症小体是一种免疫信号平台，在病原体识别后组装。它激活蛋白酶，尤其是 caspase-1，其通过蛋白水解成熟并促进成熟 IL-1β 和 IL-18 的分泌。炎症小体和 caspase-1 在成熟 IL-1β 的分泌和金黄色葡萄球菌感染的成骨细胞的防御中的作用尚未得到充分研究。我们在此表明​​，使用 CRISPR-Cas9 技术生成的金黄色葡萄球菌感染的成骨细胞样 MG-63 但不是 caspase-1 敲除的CASP1 ^−/− MG-63 细胞，通过释放成熟的IL-1β。效果与应变有关。金黄色葡萄球菌缺失和补充的酚可溶性调节蛋白 (PSM) 突变体的使用证明了 PSM 在炎症小体相关的 IL-1β 产生中的关键作用。此外，我们发现CASP1 ^−/− MG-63 细胞中缺乏 caspase-1 会损害其防御功能，因为与野生型细胞相比， CASP1 ^−/− MG-63 中的细菌清除率急剧下降。我们的结果表明，成骨细胞样 MG-63 细胞通过炎症小体激活，在针对金黄色葡萄球菌感染的免疫反应中发挥重要作用，并确立了 caspase-1 在细菌清除中的关键作用。