Phosphocholine-Modified Lipooligosaccharides of Haemophilus influenzae Inhibit ATP-Induced IL-1β Release by Pulmonary Epithelial Cells.
Phosphocholine-Modified Lipooligosaccharides of Haemophilus influenzae Inhibit ATP-Induced IL-1β Release by Pulmonary Epithelial Cells.
复制标题
嗜血性流感的磷脂改性的脂肪糖抑制ATP诱导的肺上皮细胞释放IL-1β。
DOI：
10.3390/molecules23081979
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发表时间：
2018-08-08
期刊：
影响因子：
--
通讯作者：
Grau V
中科院分区：
文献类型：
--
作者：
Richter K;Koch C;Perniss A;Wolf PM;Schweda EKH;Wichmann S;Wilker S;Magel I;Sander M;McIntosh JM;Padberg W;Grau V
磷胆碱修饰的细菌细胞壁成分是毒力因子，可使免疫逃避和永久定植哺乳动物宿主，其机制尚不清楚。最近，我们证明了来自流感嗜血杆菌（一种上、下气道的机会性病原体）的游离磷胆碱（PC）和PC修饰的低脂糖（PC- los）作为非常规的尼古丁激动剂，有效抑制atp诱导的单核细胞IL-1β的释放。我们假设流感嗜血杆菌PC-LOS对肺上皮细胞和复杂肺组织有类似的作用。用大肠杆菌脂多糖对人肺癌源性上皮细胞系A549和Calu-3进行引物，然后用ATP刺激，分别在PC存在或不存在、PC-LOS或缺乏PC的LOS的情况下刺激。使用特异性拮抗剂检测烟碱乙酰胆碱受体的参与。我们证明了PC和PC- los通过含有α7、α9和/或α10亚基的烟碱乙酰胆碱受体有效地抑制atp介导的A549和Calu-3细胞释放IL-1β。启动精确切割的肺切片表现相似。我们得出结论，流感嗜血杆菌劫持了肺部内源性抗炎胆碱能控制机制，以逃避宿主的先天免疫反应。这些发现可能为以宿主为中心的抗生素治疗慢性呼吸道感染流感嗜血杆菌铺平道路。
Phosphocholine-modified bacterial cell wall components are virulence factors enabling immune evasion and permanent colonization of the mammalian host, by mechanisms that are poorly understood. Recently, we demonstrated that free phosphocholine (PC) and PC-modified lipooligosaccharides (PC-LOS) from Haemophilus influenzae, an opportunistic pathogen of the upper and lower airways, function as unconventional nicotinic agonists and efficiently inhibit the ATP-induced release of monocytic IL-1β. We hypothesize that H. influenzae PC-LOS exert similar effects on pulmonary epithelial cells and on the complex lung tissue. The human lung carcinoma-derived epithelial cell lines A549 and Calu-3 were primed with lipopolysaccharide from Escherichia coli followed by stimulation with ATP in the presence or absence of PC or PC-LOS or LOS devoid of PC. The involvement of nicotinic acetylcholine receptors was tested using specific antagonists. We demonstrate that PC and PC-LOS efficiently inhibit ATP-mediated IL-1β release by A549 and Calu-3 cells via nicotinic acetylcholine receptors containing subunits α7, α9, and/or α10. Primed precision-cut lung slices behaved similarly. We conclude that H. influenzae hijacked an endogenous anti-inflammatory cholinergic control mechanism of the lung to evade innate immune responses of the host. These findings may pave the way towards a host-centered antibiotic treatment of chronic airway infections with H. influenzae.
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DOI：
10.1084/jem.20171848
发表时间：
2017-11-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Lamkanfi M;Dixit VM
通讯作者：
Dixit VM
影响因子：
8.7
作者：
Dinarello CA
通讯作者：
Dinarello CA
影响因子：
4.4
作者：
Hecker, Andreas;Kuellmar, Mira;Grau, Veronika
通讯作者：
Grau, Veronika
影响因子：
3.6
作者：
Baker, ER;Zwart, R;Millar, NS
通讯作者：
Millar, NS
DOI：
10.1111/j.1574-695x.2002.tb00628.x
发表时间：
2002-11-15
影响因子：
--
作者：
Humphries, HE;High, NJ
通讯作者：
High, NJ