Induced Pluripotent Stem Cell (iPSC)-Derived Endothelial Cells to Study Bacterial-Brain Endothelial Cell Interactions

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.