Epithelial cells are sensitive detectors of bacterial pore-forming toxins
Epithelial cells are sensitive detectors of bacterial pore-forming toxins
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DOI：
10.1074/jbc.m511431200
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发表时间：
2006-05-05
影响因子：
4.8
通讯作者：
Weiser, JN
中科院分区：
文献类型：
--
作者：
Ratner, AJ;Hippe, KR;Weiser, JN
上皮细胞在人体粘膜表面和周围环境之间起着界面作用。因此，它们负责启动局部免疫反应，这可能是预防侵袭性感染的关键。在这里，我们显示，上皮细胞检测到纳摩尔浓度的细菌致孔毒素(包括肺炎链球菌的肺炎溶血素、金黄色葡萄球菌的甲型溶血素、化脓性链球菌的溶血素O和炭疽杆菌的溶炭素O)，远远低于引起细胞溶解所需的浓度。P38MAPK的磷酸化似乎是上皮细胞对细菌致孔毒素的亚细胞溶解浓度的保守反应，这种活性被细胞外介质中加入高相对分子质量的渗透压所抑制。通过感知由膜中插入亚致死数量的毛孔而引起的渗透压力，上皮细胞可以作为一个早期预警系统来开始免疫反应，而产生毒素的细菌的局部密度仍然很低。因此，渗透传感可能代表了对常见细菌毒力策略的一种新的先天免疫反应。
Epithelial cells act as an interface between human mucosal surfaces and the surrounding environment. As a result, they are responsible for the initiation of local immune responses, which may be crucial for prevention of invasive infection. Here we show that epithelial cells detect the presence of bacterial pore-forming toxins ( including pneumolysin from Streptococcus pneumoniae, alpha-hemolysin from Staphylococcus aureus, streptolysin O from Streptococcus pyogenes, and anthrolysin O from Bacillus anthracis) at nanomolar concentrations, far below those required to cause cytolysis. Phosphorylation of p38 MAPK appears to be a conserved response of epithelial cells to subcytolytic concentrations of bacterial pore-forming toxins, and this activity is inhibited by the addition of high molecular weight osmolytes to the extracellular medium. By sensing osmotic stress caused by the insertion of a sublethal number of pores into their membranes, epithelial cells may act as an early warning system to commence an immune response, while the local density of toxin-producing bacteria remains low. Osmosensing may thus represent a novel innate immune response to a common bacterial virulence strategy.