Department of Biological Sciences, University of Alabama, Tuscaloosa, AL, USA.
Jacksonville State University, Jacksonville, AL, USA.
Methods Mol Biol. 2022;2492:73-101. doi: 10.1007/978-1-0716-2289-6_4.
Bacterial meningitis is a serious infection of the central nervous system (CNS) that occurs when blood-borne bacteria are able to exit the cerebral vasculature and cause inflammation. The blood-brain barrier (BBB) and the meningeal blood-CSF barrier (mBCSFB) are composed of highly specialized brain endothelial cells (BECs) that possess unique phenotypes when compared to their peripheral endothelial counterparts. To cause meningitis, bacterial pathogens must be able to interact and penetrate these specialized BECs to gain access to the CNS. In vitro models have been employed to study bacterial-BEC interactions; however, many lack BEC phenotypes. Induced pluripotent stem cell (iPSC) technologies have enabled the derivation of brain endothelial-like cells that phenocopy BECs in culture. Recently, these iPSC-BECs have been employed to examine the host-pathogen interaction at the endothelial brain barriers. Using two clinically relevant human meningeal pathogens, this chapter describes the use of iPSC-BECs to study various aspects of BEC-bacterial interaction.
细菌性脑膜炎是一种严重的中枢神经系统（CNS）感染，当血液中的细菌能够离开脑血管并引起炎症时就会发生。血脑屏障（BBB）和脑膜血脑脊液屏障（mBCSFB）由高度特化的脑内皮细胞（BEC）组成，与外周内皮细胞相比，它们具有独特的表型。为了引起脑膜炎，细菌病原体必须能够与这些特化的 BEC 相互作用并穿透它们，才能进入 CNS。体外模型已被用于研究细菌-BEC 相互作用；然而，许多模型缺乏 BEC 表型。诱导多能干细胞（iPSC）技术使脑内皮样细胞的衍生成为可能，这些细胞在培养中可模拟 BEC。最近，这些 iPSC-BEC 被用于研究内皮脑屏障中的宿主-病原体相互作用。本文使用两种临床相关的人类脑膜病原体，描述了使用 iPSC-BEC 研究 BEC-细菌相互作用的各个方面。
