School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, LE12 5RD, UK.
Exp Parasitol. 2012 Nov;132(3):367-72. doi: 10.1016/j.exppara.2012.08.012. Epub 2012 Sep 1.
Acanthamoeba granulomatous encephalitis (AGE), caused by Acanthamoeba castellanii, is a fatal infection of immunocompromised individuals. The pathogenesis of blood-brain barrier (BBB) breach remains unknown. Using a novel in vitro BBB infection model under flow conditions, demonstrates that increases in flow rates lead to decreased binding of A. castellanii to host cells. This is a distinct departure from previous findings under static conditions. However, similarly to static conditions binding of A. castellanii to host cells is host mannose dependent. Disruption of the host cell monolayer was independent of amoeba binding, but dependent on secreted serine proteases. For the first time we report the binding dynamics of A. castellanii under physiological conditions, showing that BBB disruption is not directly linked to binding, instead it is reliant on secreted proteases. Our results offer a platform on which therapies designed at modulating physiological parameters can improve the outcome of infection with A. castellanii.
棘阿米巴性肉芽肿脑炎（AGE）是由棘阿米巴原虫引起的，是免疫功能低下者的致死性感染。血脑屏障（BBB）破裂的发病机制尚不清楚。本研究采用新型体外 BBB 感染模型，在流动条件下证明，随着流速的增加，棘阿米巴原虫与宿主细胞的结合减少。这与静态条件下的先前发现明显不同。然而，与静态条件类似，棘阿米巴原虫与宿主细胞的结合依赖于宿主甘露糖。宿主细胞单层的破坏与阿米巴的结合无关，但依赖于分泌的丝氨酸蛋白酶。我们首次在生理条件下报告了棘阿米巴原虫的结合动力学，表明 BBB 破坏与结合无关，而是依赖于分泌的蛋白酶。我们的研究结果为设计调节生理参数的治疗方法提供了一个平台，这些方法可以改善感染棘阿米巴原虫的预后。
