PDF(Pubmed)
Abstract：
Bacterial pleural infections are associated with high mortality. Treatment is complicated due to biofilm formation. A common causative pathogen is Staphylococcus aureus (S. aureus). Since it is distinctly human-specific, rodent models do not provide adequate conditions for research. The purpose of this study was to examine the effects of S. aureus infection on human pleural mesothelial cells using a recently established 3D organotypic co-culture model of pleura derived from human specimens. After infection of our model with S. aureus, samples were harvested at defined time points. Histological analysis and immunostaining for tight junction proteins (c-Jun, VE-cadherin, and ZO-1) were performed, demonstrating changes comparable to in vivo empyema. The measurement of secreted cytokine levels (TNF-α, MCP-1, and IL-1β) proved host-pathogen interactions in our model. Similarly, mesothelial cells produced VEGF on in vivo levels. These findings were contrasted by vital, unimpaired cells in a sterile control model. We were able to establish a 3D organotypic in vitro co-culture model of human pleura infected with S. aureus resulting in the formation of biofilm, including host-pathogen interactions. This novel model could be a useful microenvironment tool for in vitro studies on biofilm in pleural empyema.
摘要：
细菌性胸膜感染与高死亡率相关。由于生物膜形成,治疗是复杂的。常见的致病病原体是金黄色葡萄球菌(S.金黄色葡萄球菌）。因为它明显是人类特有的，啮齿动物模型不能为研究提供足够的条件。这项研究的目的是使用最近建立的源自人类样本的胸膜的3D器官型共培养模型来检查金黄色葡萄球菌感染对人胸膜间皮细胞的影响。我们的模型感染金黄色葡萄球菌后，在确定的时间点收获样品。紧密连接蛋白的组织学分析和免疫染色（c-Jun，VE-钙黏着蛋白,和ZO-1)进行，表现出与体内脓胸相当的变化。分泌的细胞因子水平的测量(TNF-α，MCP-1和IL-1β）在我们的模型中证明了宿主-病原体的相互作用。同样，间皮细胞在体内水平上产生VEGF。这些发现与重要的，无菌对照模型中的未受损细胞。我们能够建立一个3D器官型体外共培养模型的人胸膜感染金黄色葡萄球菌，导致生物膜的形成，包括宿主-病原体相互作用。这种新型模型可能是一种有用的微环境工具，可用于胸膜脓胸中生物膜的体外研究。
