滑膜巨噬细胞的训练免疫与金黄色葡萄球菌感染后关节炎症和损伤加剧有关。

IF 4.8 3区 医学 Q2 CELL BIOLOGY Inflammation Research Pub Date : 2024-11-01 Epub Date: 2024-09-28 DOI:10.1007/s00011-024-01946-w
Peter Silva Rocha, Adryan Aparecido Silva, Celso Martins Queiroz-Junior, Amanda Dias Braga, Thaiane Pinto Moreira, Mauro Martins Teixeira, Flávio Almeida Amaral
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引用次数: 0

摘要

目的:研究滑膜细胞是否会获得训练有素的免疫特性,从而在继发金黄色葡萄球菌感染后加剧关节炎症:研究滑膜细胞是否以及哪些滑膜细胞会获得训练有素的免疫特性,从而在继发金黄色葡萄球菌感染后加剧关节炎症:方法:在雄性C57BL/6小鼠的胫股关节腔内分别或同时注射脂多糖(LPS)和金黄色葡萄球菌(间隔21天)。在这些刺激后的不同时间点,对机械痛觉进行分析,然后分析受影响关节的炎症和损伤迹象。在整个组织或分离的滑膜细胞中分析了训练有素的免疫标记物,包括糖酵解和 mTOR 通路。一组小鼠在接受 LPS 或金黄色葡萄球菌刺激前使用了 mTOR 抑制剂雷帕霉素:结果:与单关节刺激相比,LPS - 金黄色葡萄球菌双重刺激会加剧关节炎症和损伤,包括滑膜细胞活化、促炎细胞因子的产生、持续痛觉和骨损伤,尽管细菌清除率并没有降低。LPS - 金黄色葡萄球菌双击关节增加了表达 CX3CR1 的滑膜巨噬细胞数量,同时引发了与这些细胞中训练有素的免疫事件相关的既定表观遗传修饰,如 mTOR 信号通路(p-mTOR 和 HIF1α)的上调和组蛋白 H3 的三甲基化。使用雷帕霉素治疗的小鼠减少了CX3CR1+巨噬细胞的活化、关节炎症和骨损伤:结论:在由金黄色葡萄球菌引起的化脓性关节炎期间,CX3CR1+滑膜巨噬细胞中存在一种训练有素的免疫表型,有助于关节炎症和损伤的加重。
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Trained immunity of synovial macrophages is associated with exacerbated joint inflammation and damage after Staphylococcus aureus infection.

Objectives: Investigate whether and which synoviocytes would acquire trained immunity characteristics that could exacerbate joint inflammation following a secondary Staphylococcus aureus infection.

Methods: Lipopolysaccharide (LPS) and S. aureus were separately or double injected (21 days of interval) into the tibiofemoral joint cavity of male C57BL/6 mice. At different time points after these stimulations, mechanical nociception was analyzed followed by the analysis of signs of inflammation and damage in the affected joints. The trained immunity markers, including the glycolytic and mTOR pathway, were analyzed in whole tissue or isolated synoviocytes. A group of mice was treated with Rapamycin, an mTOR inhibitor before LPS or S. aureus stimulation.

Results: The double LPS - S. aureus hit promoted intense joint inflammation and damage compared to single joint stimulation, including markers in synoviocyte activation, production of proinflammatory cytokines, persistent nociception, and bone damage, despite not reducing the bacterial clearance. The double LPS - S. aureus hit joints increased the synovial macrophage population expressing CX3CR1 alongside triggering established epigenetic modifications associated with trained immunity events in these cells, such as the upregulation of the mTOR signaling pathway (p-mTOR and HIF1α) and the trimethylation of histone H3. Mice treated with Rapamycin presented reduced CX3CR1+ macrophage activation, joint inflammation, and bone damage.

Conclusions: There is a trained immunity phenotype in CX3CR1+ synovial macrophages that contributes to the exacerbation of joint inflammation and damage during septic arthritis caused by S. aureus.

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来源期刊
Inflammation Research
Inflammation Research 医学-免疫学
CiteScore
9.90
自引率
1.50%
发文量
134
审稿时长
3-8 weeks
期刊介绍: Inflammation Research (IR) publishes peer-reviewed papers on all aspects of inflammation and related fields including histopathology, immunological mechanisms, gene expression, mediators, experimental models, clinical investigations and the effect of drugs. Related fields are broadly defined and include for instance, allergy and asthma, shock, pain, joint damage, skin disease as well as clinical trials of relevant drugs.
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