Interactions of Haemophilus parasuis and its LOS with porcine brain microvascular endothelial cells

Interactions of Haemophilus parasuis and its LOS with porcine brain microvascular endothelial cells
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DOI:
10.1051/vetres:2008019
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发表时间:
2008-09-01
影响因子:
4.4
通讯作者:
Gottschalk, Marcelo
Gottschalk, Marcelo
中科院分区:
农林科学2区
文献类型:
--
作者:
Bouchet, Benedicte;Vanier, Ghyslaine;Gottschalk, Marcelo

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副猪嗜血杆菌是一种猪病原体,可引起以多浆液炎和脑膜炎为特征的格拉瑟病。副猪嗜血杆菌感染的发病机制尚不清楚。为了引起脑膜炎,副猪嗜血杆菌必须穿过血脑屏障(BBB)进入中枢神经系统(CNS)。我们最近发现副猪嗜血杆菌附着并侵入猪脑微血管内皮细胞(PBMEC)。本研究的目的是评估副猪嗜血杆菌低脂寡糖(LOS)在PBMEC粘附中的作用,并确定副猪嗜血杆菌(和/或其LOS)是否能够诱导PBMEC的凋亡和激活。结果表明,副猪嗜血杆菌对PBMEC的粘附部分介导了LOS的作用。此外,副猪嗜血杆菌诱导caspase-3介导的PBMEC凋亡具有时间和剂量依赖性,但其LOS似乎没有参与这一过程。此外,副猪嗜血杆菌及其LOS(在较小程度上)能够诱导PBMEC释放IL-8和IL-6。副猪嗜血杆菌血清型4和5的野外菌株诱导了相似水平的这些炎症介质。我们的数据提示副猪绦虫通过血脑屏障通过细胞粘附、诱导细胞凋亡和上调炎症介质侵袭中枢神经系统,而LOS在这一病理过程中可能发挥一定但有限的作用。
Haemophilus parasuis is a swine pathogen that causes Glasser's disease, which is characterized by polyserositis and meningitis. The pathogenesis of the H. parasuis infection is poorly understood. To cause meningitis, H. parasuis has to cross the blood-brain barrier (BBB) to gain access to the central nervous system (CNS). We recently showed that H. parasuis adheres to and invades porcine brain microvascular endothelial cells (PBMEC). The aim of this study was to evaluate the role of H. parasuis lipooligosaccharide (LOS) in the adhesion to PBMEC and to determine if H. parasuis (and/or its LOS) is able to induce apoptosis and activation of PBMEC. Results showed that adhesion of H. parasuis to PBMEC was partially mediated by LOS. Moreover, H. parasuis induces caspase-3-mediated apoptosis of PBMEC in a time - and dose dependent manner, but its LOS did not seem to be involved in such a process. Furthermore, H. parasuis and, to a lesser extent, its LOS, was able to induce the release of IL-8 and IL-6 by PBMEC. Field strains of H. parasuis serotypes 4 and 5 induced similar levels of these inflammatory mediators. Our data suggest that H. parasuis uses cellular adhesion, induction of apoptosis and up-regulation of inflammatory mediators as mechanisms to invade the CNS via the BBB, and that LOS would play a certain but limited role in such pathological process.