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Biofilm-Infected Intracerebroventricular Shunts Elicit Inflammation within the Central Nervous System

机译:生物膜感染的脑室内分流诱发中枢神经系统内的炎症

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Central nervous system catheter infections are a serious complication in the treatment of hydrocephalus. These infections are commonly caused by Staphylococcus epidermidis and Staphylococcus aureus, both known to form biofilms on the catheter surface. Our objective was to generate a novel murine model of central nervous system catheter-associated biofilm infection using a clinical S. aureus isolate and characterize the nature of the inflammatory response during biofilm growth. Silicone catheters were precoated with S. aureus to facilitate bacterial attachment, whereupon infected or sterile catheters were stereotactically inserted into the lateral ventricle of the brain in C57BL/6 mice and evaluated at regular intervals through day 21 postinsertion. Animals tolerated the procedure well, with no clinical signs of illness or bacterial growth seen in the control group. Bacterial titers associated with central nervous system catheters were significantly elevated compared to those from the surrounding parenchyma, consistent with biofilm formation and minimal planktonic spread of infection. Catheter-associated bacterial burdens progressively increased, with maximal colonization achieved at day 7 postinfection. Analysis of inflammatory infiltrates by fluorescence-activated cell sorting (FACS) revealed significant macrophage and neutrophil influx, which peaked at days 3 and 5 to 7, respectively. In contrast, there were no detectable immune infiltrates associated with tissues surrounding sterile catheters. Biofilm infection led to significant increases in chemokine (CXCL1 and CCL2) and proinflammatory cytokine (interleukin 17 [IL-17]) expression in tissues surrounding infected central nervous system catheters. Based on these results, we propose this approach is a valid animal model for further investigations of catheter-associated central nervous system shunt infections.
机译:中枢神经系统导管感染是脑积水的严重并发症。这些感染通常是由表皮葡萄球菌和金黄色葡萄球菌引起的,都已知会在导管表面形成生物膜。我们的目标是使用临床金黄色葡萄球菌分离物生成中枢神经系统导管相关生物膜感染的新型鼠模型,并表征生物膜生长过程中炎症反应的性质。硅胶导管预先涂有金黄色葡萄球菌,以促进细菌附着,随后将感染的或无菌导管立体定向插入C57BL / 6小鼠的大脑侧脑室,并在插入后第21天定期进行评估。动物对手术的耐受性很好,对照组没有发现疾病或细菌生长的临床迹象。与来自周围薄壁组织的细菌滴度相比,与中枢神经系统导管相关的细菌滴度显着升高,这与生物膜的形成和感染的浮游扩散最小有关。与导管相关的细菌负担逐渐增加,在感染后第7天达到最大定植。通过荧光激活细胞分选术(FACS)对炎性浸润进行分析,发现巨噬细胞和中性粒细胞大量涌入,分别在第3天和第5至7天达到高峰。相反,没有检测到与无菌导管周围组织相关的免疫浸润。生物膜感染导致受感染的中枢神经系统导管周围组织中的趋化因子(CXCL1和CCL2)和促炎性细胞因子(白介素17 [IL-17])表达显着增加。根据这些结果,我们认为该方法是用于进一步研究导管相关中枢神经系统分流感染的有效动物模型。

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