Institute of Anatomy, University of Bern, Baltzerstrasse 2, 3012, Bern, Switzerland.
Institute for Infectious Diseases, University of Bern, Friedbühlstrasse 51, 3010, Bern, Switzerland.
J Neuroinflammation. 2019 May 18;16(1):105. doi: 10.1186/s12974-019-1491-7.
Streptococcus pneumoniae is the cause of a highly lethal form of meningitis in humans. Microglial cells in the brain represent the first line of defense against pathogens, and they participate in the inflammatory response. The cholesterol-dependent cytolysin pneumolysin and the bacterial capsule are key pathogenic factors, known to exacerbate the course of pneumococcal meningitis.
We utilized live imaging and immunostaining of glial cells in dissociated and acute brain slice cultures to study the effect of pneumococcal factors, including the cholesterol-dependent cytolysin pneumolysin and the pneumococcal capsule, on microglial motility and taxis.
In brain tissue, primary microglia cells showed an enhanced response towards lysates from bacteria lacking capsules and pneumolysin as they moved rapidly to areas with an abundance of bacterial factors. The presence of bacterial capsules and pneumolysin cumulatively inhibited microglial taxis. In mixed cultures of astrocytes and microglia, the motility of microglia was inhibited by capsular components within minutes after exposure. The reduced motility was partially reversed by mannan, a mannose receptor inhibitor. The effects on microglia were not mediated by astrocytes because pure microglial cells responded to various pneumococcal lysates similarly with distinct cell shape changes as seen in mixed cultures.
Our data indicate that microglia possess the capacity for a very agile response towards bacterial pathogens, but key pathogenic factors, such as pneumococcal capsules and pneumolysin, inhibited this response shortly after a bacterial challenge. Furthermore, we demonstrate for the first time that the bacterial capsule affects cellular behaviors such as motility and taxis.
肺炎链球菌是导致人类高度致命性脑膜炎的病原体。大脑中的小胶质细胞是抵御病原体的第一道防线，它们参与炎症反应。胆固醇依赖性细胞溶素肺炎球菌溶血素和细菌荚膜是关键的致病因素，已知它们会加剧肺炎球菌性脑膜炎的病程。
我们利用分离和急性脑片培养中的神经胶质细胞的活体成像和免疫染色来研究肺炎球菌因子（包括胆固醇依赖性细胞溶素肺炎球菌溶血素和肺炎球菌荚膜）对小胶质细胞运动和趋化性的影响。
在脑组织中，初级小胶质细胞对缺乏荚膜和肺炎球菌溶血素的细菌裂解物表现出增强的反应，因为它们迅速移动到富含细菌因子的区域。细菌荚膜和肺炎球菌溶血素的存在会累积抑制小胶质细胞的趋化性。在星形胶质细胞和小胶质细胞的混合培养中，暴露于细菌成分后，小胶质细胞的运动在数分钟内被抑制。甘露聚糖，一种甘露糖受体抑制剂，部分逆转了这种抑制作用。这些作用不是通过星形胶质细胞介导的，因为在混合培养中，纯小胶质细胞对各种肺炎球菌裂解物的反应相似，表现出明显的细胞形态变化。
我们的数据表明，小胶质细胞具有对细菌病原体非常敏捷的反应能力，但关键的致病因素，如肺炎球菌荚膜和肺炎球菌溶血素，在细菌攻击后不久就抑制了这种反应。此外，我们首次证明细菌荚膜会影响细胞行为，如运动和趋化性。
Zotero 插件
