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Reversible Inhibition of Chlamydia trachomatis Infection in Epithelial Cells Due to Stimulation of P2X4 Receptors

机译:由于刺激P2X4受体,沙眼衣原体感染在上皮细胞中的可逆抑制作用。

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Bacterial infections of the mucosal epithelium are a major cause of human disease. The prolonged presence of microbial pathogens stimulates inflammation of the local tissues, which leads to changes in the molecular composition of the extracellular milieu. A well-characterized molecule that is released to the extracellular milieu by stressed or infected cells is extracellular ATP and its ecto-enzymatic degradation products, which function as signaling molecules through ligation of purinergic receptors. There has been little information, however, on the effects of the extracellular metabolites on bacterial growth in inflamed tissues. Millimolar concentrations of ATP have been previously shown to inhibit irreversibly bacterial infection through ligation of P2X7 receptors. We show here that the proinflammatory mediator, ATP, is released from Chlamydia trachomatis-infected epithelial cells. Moreover, further stimulation of the infected cells with micromolar extracellular ADP or ATP significantly impairs the growth of the bacteria, with a profile characteristic of the involvement of P2X4 receptors. A specific role for P2X4 was confirmed using cells overexpressing P2X4. The chlamydiae remain viable and return to normal growth kinetics after removal of the extracellular stimulus, similar to responses previously described for persistence of chlamydial infection.
机译:粘膜上皮的细菌感染是人类疾病的主要原因。微生物病原体的长期存在会刺激局部组织的炎症,从而导致细胞外环境的分子组成发生变化。被应激或感染的细胞释放到细胞外环境中的一个特征明确的分子是细胞外ATP及其外酶降解产物,其通过嘌呤能受体的连接起信号分子的作用。但是,关于细胞外代谢物对发炎组织中细菌生长的影响的信息很少。先前已显示,毫摩尔浓度的ATP通过连接P2X7受体抑制不可逆的细菌感染。我们在这里显示促炎介质,ATP,从沙眼衣原体感染的上皮细胞中释放。此外,用微摩尔细胞外ADP或ATP进一步刺激感染的细胞会显着损害细菌的生长,并具有P2X4受体参与的特征。使用过表达P2X4的细胞证实了P2X4的特定作用。去除衣原体刺激后,衣原体仍能存活并恢复正常的生长动力学,类似于先前描述的衣原体感染持续存在的反应。

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