Streptococcus suis serotype 2 interactions with human brain microvascular endothelial cells

Streptococcus suis serotype 2 interactions with human brain microvascular endothelial cells
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DOI:
10.1128/iai.68.2.637-643.2000
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发表时间:
2000-02-01
影响因子:
3.1
通讯作者:
Gottschalk, M
Gottschalk, M
中科院分区:
医学2区
文献类型:
--
作者:
Charland, N;Nizet, V;Gottschalk, M

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猪链球菌血清2型是一种世界范围内的多种猪感染病原体,也被认为是一种引起人类疾病的人畜共患病原体,包括脑膜炎。猪链球菌感染的发病机制尚不清楚。细菌在无免疫宿主的血液中循环,直到它们与形成血脑屏障的脑微血管内皮细胞(BMEC)接触。细菌多糖胶囊具有抗吞噬特性。已知B群链球菌(GBS)侵入并破坏BMEC,这可能是新生儿脑膜炎发病的第一步。研究了猪链球菌与人内皮细胞之间的相互作用,以确定它们是否与GBS和内皮细胞之间的相互作用不同。用BMEC和人脐静脉内皮细胞进行的侵袭试验表明,与GBS, S不同,猪链球菌血清型2不能侵袭任何一种细胞。粘附实验表明,S, suis仅粘附在BMEC上,而GBS粘附在两种类型的细胞上。这些相互作用不受胶囊存在的影响,因为来自两种细菌的胶囊突变体与野生型菌株的粘附性相似。乳酸脱氢酶释放测试表明,一些猪链球菌菌株对BMEC具有很高的细胞毒性,甚至超过GBS,而其他菌株则完全没有毒性。细胞损伤与产生溶血素有关,因为只有产生溶血素的菌株具有细胞毒性,而细胞毒性可以被胆固醇和抗溶血素抗体抑制。溶血素阳性S,猪毒株可能利用黏附性和溶血素诱导的BMEC损伤,而不是直接细胞入侵,从循环系统进入中枢神经系统。
Streptococcus suis serotype 2 is a worldwide causative agent of many forms of swine infection and is also recognized as a zoonotic agent causing human disease, including meningitis. The pathogenesis of S, suis infections is poorly understood. Bacteria circulate in the bloodstream in the nonimmune host until they come in contact with brain microvascular endothelial cells (BMEC) forming the blood-brain barrier. The bacterial polysaccharide capsule confers antiphagocytic properties. It is known that group B streptococci (GBS) invade and damage BMEC, which may be a primary step in the pathogenesis of neonatal meningitis. Interactions between S, suis and human endothelial cells were studied to determine if they differ from those between GBS and endothelial cells, Invasion assays performed with BMEC and human umbilical vein endothelial cells demonstrated that unlike GBS, S, suis serotype 2 could not invade either type of cell. Adherence assays showed that S, suis adhered only to BMEC, whereas GBS adhered to both types of cell. These interactions were not affected by the presence of a capsule, since acapsular mutants from both bacterial species adhered similarly compared to the wild-type strains. Lactate dehydrogenase release measurements indicated that some S. suis strains were highly cytotoxic for BMEC, even more than GBS, whereas others were not toxic at all. Cell damage was related to suilysin (S.suis hemolysin) production, since only suilysin-producing strains were cytotoxic and cytotoxicity could be inhibited by cholesterol and antisuilysin antibodies. It is possible that hemolysin-positive S, suis strains use adherence and suilysin-induced BMEC injury, as opposed to direct cellular invasion, to proceed from the circulation to the central nervous system.