Gianinazzi C, Schild M, Müller N, Leib S L, Simon F, Nuñez S, Joss P, Gottstein B
Institute of Parasitology, University of Bern, Länggass-Strasse 122, CH-3001 Bern, Switzerland.
Parasitology. 2005 Dec;131(Pt 6):797-804. doi: 10.1017/S0031182005008619.
The free-living amoeba Naegleria fowleri is the aetiological agent of primary amoebic meningoencephalitis (PAM), a disease leading to death in the vast majority of cases. In patients suffering from PAM, and in corresponding animal models, the brain undergoes a massive inflammatory response, followed by haemorrhage and severe tissue necrosis. Both, in vivo and in vitro models are currently being used to study PAM infection. However, animal models may pose ethical issues, are dependent upon availability of specific infrastructural facilities, and are time-consuming and costly. Conversely, cell cultures lack the complex organ-specific morphology found in vivo, and thus, findings obtained in vitro do not necessarily reflect the situation in vivo. The present study reports infection of organotypic slice cultures from rat brain with N. fowleri and compares the findings in this culture system with in vivo infection in a rat model of PAM, that proved complementary to that of mice. We found that brain morphology, as present in vivo, is well retained in organotypic slice cultures, and that infection time-course including tissue damage parallels the observations in vivo in the rat. Therefore, organotypic slice cultures from rat brain offer a new in vitro approach to study N. fowleri infection in the context of PAM.
自由生活的阿米巴原虫福氏耐格里阿米巴是原发性阿米巴脑膜脑炎（PAM）的病原体，这种疾病在绝大多数病例中都会导致死亡。在患有PAM的患者以及相应的动物模型中，大脑会发生大规模炎症反应，随后出现出血和严重的组织坏死。目前，体内和体外模型都被用于研究PAM感染。然而，动物模型可能会带来伦理问题，依赖于特定基础设施的可用性，并且耗时且成本高昂。相反，细胞培养缺乏体内发现的复杂器官特异性形态，因此，体外获得的结果不一定反映体内情况。本研究报告了福氏耐格里阿米巴对大鼠脑器官型切片培养物的感染，并将该培养系统中的结果与PAM大鼠模型中的体内感染结果进行了比较，结果证明该模型与小鼠模型具有互补性。我们发现，体内存在的脑形态在器官型切片培养物中得到了很好的保留，并且包括组织损伤在内的感染时间进程与大鼠体内的观察结果相似。因此，大鼠脑器官型切片培养物提供了一种新的体外方法，用于在PAM背景下研究福氏耐格里阿米巴感染。
