Reduction of Pertussis Inflammatory Pathology by Therapeutic Treatment With Sphingosine-1-Phosphate Receptor Ligands by a Pertussis Toxin-Insensitive Mechanism.
Reduction of Pertussis Inflammatory Pathology by Therapeutic Treatment With Sphingosine-1-Phosphate Receptor Ligands by a Pertussis Toxin-Insensitive Mechanism.
复制标题
通过百日咳毒素不敏感机制使用 1-磷酸鞘氨醇受体配体进行治疗，可减少百日咳炎症病理。
DOI：
10.1093/infdis/jiw536
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Carbonetti,NicholasH
中科院分区：
文献类型：
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作者：
Skerry,Ciaran;Scanlon,Karen;Ardanuy,Jeremy;Roberts,Drew;Zhang,Li;Rosen,Hugh;Carbonetti,NicholasH
最近的数据证明了 1-磷酸鞘氨醇 (S1P) 受体 (S1PR) 激动剂在治疗传染病方面的潜力。先前的一项研究使用百日咳博德特氏菌感染的小鼠模型来证明，使用 S1PR 激动剂 AAL-R 治疗可减少感染期间的肺部炎症。在当前的研究中，我们表明这种效应是通过 LysM+（骨髓）细胞上的 S1PR1 介导的。通过该受体发出的信号可减少新生小鼠疾病模型中的肺部炎症和细胞募集，并降低发病率和死亡率。尽管 S1PR 是百日咳毒素敏感的 G 蛋白偶联受体，但在我们的模型中，AAL-R 的作用对百日咳毒素不敏感。此外，我们的数据表明，S1PR 激动剂给药可能在治疗时间点有效。这些结果表明 S1P 信号传导在 B 中的作用。百日咳介导的病理学并强调了针对百日咳的宿主靶向治疗的可能性。
Recent data have demonstrated the potential of sphingosine 1-phosphate (S1P) receptor (S1PR) agonism in the treatment of infectious diseases. A previous study used a murine model ofBordetella pertussisinfection to demonstrate that treatment with the S1PR agonist AAL-R reduces pulmonary inflammation during infection. In the current study, we showed that this effect is mediated via the S1PR1 on LysM+(myeloid) cells. Signaling via this receptor results in reduced lung inflammation and cellular recruitment as well as reduced morbidity and mortality in a neonatal mouse model of disease. Despite the fact that S1PRs are pertussis toxin–sensitive G protein-coupled receptors, the effects of AAL-R were pertussis toxin insensitive in our model. Furthermore, our data demonstrate that S1PR agonist administration may be effective at therapeutic time points. These results indicate a role for S1P signaling inB. pertussis–mediated pathology and highlight the possibility of host-targeted therapy for pertussis.