猪链球菌对体外血-脑脊液屏障的菌株依赖性破坏

Tobias Tenenbaum , Rüdiger Adam , Ingo Eggelnpöhler , David Matalon , Annette Seibt , Gerd E. K. Novotny , Hans-Joachim Galla , Horst Schroten
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引用次数: 51

摘要

猪链球菌荚膜2型是引起猪脑膜炎等疾病的重要病原体,也是一种人畜共患病原体。构成血脑脊液屏障结构基础的脉络膜丛上皮的屏障功能在细菌性脑膜炎中尚未阐明。我们研究了不同猪链球菌分离株对培养的猪脉络膜丛上皮细胞屏障功能的影响,包括经上皮抗性和细胞旁[3H]-甘露醇通量。优先根尖应用猪链球菌分离株可显著降低经上皮耐药,显著增加细胞旁[3H]-甘露醇通量,且呈时间、剂量和菌株依赖关系。乳酸脱氢酶测定和电镜检测结果表明,活猪链球菌具有细胞毒性,而超声猪链球菌和紫外线灭活猪链球菌不具有细胞毒性。观察到的猪脉络膜丛上皮细胞屏障功能的影响不能完全归因于猪链球菌的已知毒力因子,如尿素。总之,猪链球菌分离物在体外模型中诱导血脑脊髓液屏障功能丧失。因此,猪链球菌可能促进细菌和白细胞通过血-脑脊液屏障的运输。屏障破裂的潜在机制尚未确定。
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Strain-dependent disruption of blood–cerebrospinal fluid barrier by Streptoccocus suis in vitro

Streptococcus suis capsular type 2 is an important agent of diseases including meningitis among pigs worldwide, and is also a zoonotic agent. The barrier function of the choroid plexus epithelium that constitutes the structural basis for the blood-cerebrospinal fluid (CSF) barrier has not been elucidated yet in bacterial meningitis. We investigated the influence of various S. suis isolates on the barrier function of cultured porcine choroid plexus epithelial cells with respect to the transepithelial resistance and paracellular [3H]-mannitol flux. Preferentially apical application of S. suis isolates significantly decreased transepithelial resistance and significantly increased paracellular [3H]-mannitol flux in a time-, dose- and strain-dependent manner. Viable S. suis isolates caused cytotoxicity determined by lactate dehydrogenase assay and electron microscopy, whereas S. suis sonicates and UV-inactivated S. suis did not cause cytotoxicity. The observed effects on porcine choroid plexus epithelial cells barrier function could not exclusively be ascribed to known virulence factors of S. suis such as suilysin. In conclusion, S. suis isolates induce loss of blood–cerebrospinal fluid barrier function in an in vitro model. Thus, S. suis may facilitate trafficking of bacteria and leucocytes across the blood–cerebrospinal fluid barrier. The underlying mechanisms for the barrier breakdown have yet to be determined.

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