Role of Listeria monocytogenes exotoxins listeriolysin and phosphatidylinositol-specific phospholipase C in activation of human neutrophils
Role of Listeria monocytogenes exotoxins listeriolysin and phosphatidylinositol-specific phospholipase C in activation of human neutrophils
复制标题
DOI：
10.1128/iai.67.3.1125-1130.1999
复制
发表时间：
1999-03-01
影响因子：
3.1
通讯作者：
Grimminger, F
中科院分区：
文献类型：
--
作者：
Sibelius, U;Schulz, EC;Grimminger, F
多态核白细胞（PMN）是单核增生李斯特菌感染的关键，本研究探讨了李斯特菌外毒素李斯特菌溶素（LLO）和磷脂酰肌醇特异性磷脂酶C （PlcA）在人中性粒细胞活化中的作用，采用不同的李斯特菌菌株，在单个毒力基因突变，以及纯化的LLO。人类中性粒细胞与野生型单核增生乳杆菌共孵卵可引起PMN激活，独立于吞噬事件发生，同时伴随弹性酶分泌、白三烯生成、血小板活化因子（PAF）合成、呼吸爆发、磷酸肌肽水解增强、脱粒和白三烯形成仅依赖于LLO表达。因为当使用llo缺陷突变株EGD-和无毒菌株时，这些特征就不存在了。这些效应被表达LLO （INN+）的重组L无源菌株和纯化的LLO分子完全复制。PAF的合成也需要LLO的分泌。然而，野生型L单核细胞增生基因在诱导PAF形成方面比表达LLO的突变体更有效，这表明涉及其他毒力因素。这在磷酸肌苷水解和呼吸爆发中更为明显：这些事件不仅是由INN+引起的，而且是由低密度脂蛋白缺陷突变体EGD-和产生李斯特PlcA的重组L. innocua菌株引起的。我们得出的结论是，人类中性粒细胞对细胞外提供的李斯特菌外毒素的反应是通过快速的细胞激活。李斯特菌溶素主要参与触发脱颗粒和脂质介质的产生，此外，PlcA等毒力因子显然有助于触发中性粒细胞磷酸肌肽水解和呼吸破裂。通过这种方式，李斯特菌外毒素可能影响宿主对单核增生乳杆菌感染的防御。
Polymorphonuclear leukocytes (PMN) are essential for resolution of infections with Listeria monocytogenes, The present study investigated the role of the listerial exotoxins listeriolysin (LLO) and phosphatidylinositol-specific phospholipase C (PlcA) in human neutrophil activation, Different Listeria strains, mutated in individual virulence genes, as well as purified LLO were used. Coincubation of human neutrophils with wild-type L. monocytogenes provoked PMN activation, occurring independently of phagocytosis events, with concomitant elastase secretion, leukotriene generation, platelet-activating factor (PAF) synthesis, respiratory burst, and enhanced phosphoinositide hydrolysis, Degranulation and leukotriene formation were noted to be solely dependent on LLO expression, as these features were absent when the LLO-defective mutant EGD- and the avirulent strain L. innocua were used. These effects were fully reproduced by a recombinant L, innocua strain expressing LLO (INN+) and by the purified LLO molecule. LLO secretion was also required for PAF synthesis. However, wild-type L, monocytogenes was more potent in eliciting PAF formation than mutants expressing LLO, suggesting the involvement of additional virulence factors. This was even more obvious for phosphoinositide hydrolysis and respiratory burst: these events were provoked not only by INN+ but also by the LLO-defective mutant EGD- and by a recombinant L. innocua strain producing listerial PlcA. We conclude that human neutrophils react to extracellularly provided listerial exotoxins by rapid cell activation. Listeriolysin is centrally involved in triggering degranulation and lipid mediator generation, and further virulence factors such as PlcA apparently contribute to trigger neutrophil phosphoinositide hydrolysis and respiratory burst. In this way, listerial exotoxins may influence the host defense against infections with L. monocytogenes.