感染调节了有利于溶解的介质,降低了抗生素需求
Nan Chiang1, Gabrielle Fredman, Fredrik Bäckhed
1Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Nature
|April 28, 2012
概括
像resolvin D5和protein D1这样的专门的亲溶解媒介 (SPM) 通过增强细胞和减少炎症来积极解决细菌感染. 这些SPM与抗生素一起工作,以改善细菌清除和生存.
科学领域:
- 免疫学 免疫学 免疫学
- 微生物学 微生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 细菌感染引起的炎症解消的机制尚不清楚.
- 专门的亲解决媒介 (SPMs) 参与炎症解决.
- 具体的SPM在细菌感染中的作用需要进一步阐明.
研究的目的:
- 调查SPM在解决细菌感染中的作用.
- 为了确定与大肠杆菌感染有关的特定的SPM.
- 确定SPM在增强细菌清除和宿主存活方面的治疗潜力.
主要方法:
- 在小鼠腹腔内肠道大肠杆菌感染中排泄白细胞贩运和介质代谢脂类药物.
- 时间识别促炎媒介和SPM.
- 用人类中性粒细胞和巨细胞进行体外检测,以评估细胞和基因调节.
- 实体研究评估了SPM对细菌标位,低温,生存和抗生素疗效的影响.
主要成果:
- 在自我溶解的大肠杆菌感染中,Resolvin (Rv) D5和protein D1 (PD1) 被确定为主要的SPM.
- 与传统小鼠相比,在没有细菌的小鼠中观察到较高的RvD1和PD1水平.
- RvD1和RvD5降低了细菌负载,低温和增加了大肠杆菌感染中的存活率.
- RvD1,RvD5和PD1增强了人类免疫细胞对大肠杆菌的化作用.
- RvD5 反调节了促炎基因 (NF-κB,TNF-α) 并激活了GPR32受体.
- SPM加速了感染的消失,并增强了抗生素 (西普洛克萨,万科米) 对大肠杆菌和金黄色葡萄球菌的疗效.
结论:
- 在细菌感染期间,特定的SPM受到差异调节,并积极促进解决.
- SPM具有抗菌性质,增强细菌的制,减少抗生素的需求.
- 主体指导的SPM疗法有望改善细菌感染的结果,并补充抗生素治疗.
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