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Updated: Dec 13, 2025
Neisseria meningitidis Infection of Induced Pluripotent Stem-Cell Derived Brain Endothelial Cells
Published on: July 14, 2020
Neisseria meningitidis Infection of Induced Pluripotent Stem-Cell Derived Brain Endothelial Cells
Leo M Endres1, Sarah F Hathcock2, Alexandra Schubert-Unkmeir1
1Institute for Hygiene and Microbiology, University of Würzburg.
Abstract:
Meningococcal meningitis is a life-threatening infection that occurs when Neisseria meningitidis (meningococcus, Nm) can gain access to the central nervous system (CNS) by penetrating highly specialized brain endothelial cells (BECs). As Nm is a human-specific pathogen, the lack of robust in vivo model systems makes study of the host-pathogen interactions between Nm and BECs challenging and establishes a need for a human based model that mimics native BECs. BECs possess tighter barrier properties when compared to peripheral endothelial cells characterized by complex tight junctions and elevated trans-endothelial electrical resistance (TEER). However, many in vitro models, such as primary BECs and immortalized BECs, either lack or rapidly lose their barrier properties after removal from the native neural microenvironment. Recent advances in human stem-cell technologies have developed methods for deriving brain-like endothelial cells from induced pluripotent stem-cells (iPSCs) that better phenocopy BECs when compared to other in vitro human models. The use of iPSC-derived BECs (iPSC-BECs) to model Nm-BEC interaction has the benefit of using human cells that possess BEC barrier properties, and can be used to examine barrier destruction, innate immune activation, and bacterial interaction. Here we demonstrate how to derive iPSC-BECs from iPSCs in addition to bacterial preparation, infection, and sample collection for analysis.
Insights
This study introduces induced pluripotent stem-cell-derived brain endothelial cells (iPSC-BECs) as a human model to study Neisseria meningitidis (meningococcus) invasion of the central nervous system. This model overcomes limitations of previous systems for investigating host-pathogen interactions.
Area of Science:
- Neuroscience
- Infectious Diseases
- Cell Biology
Background:
- Meningococcal meningitis is a severe CNS infection caused by Neisseria meningitidis (Nm).
- Studying Nm interaction with brain endothelial cells (BECs) is crucial but challenging due to lack of adequate human in vivo models.
- Existing in vitro BEC models often fail to replicate native barrier properties.
Purpose of the Study:
- To develop and validate a human-based in vitro model using iPSC-derived BECs (iPSC-BECs) for studying Nm-BEC interactions.
- To provide a method for deriving iPSC-BECs and preparing for Nm infection studies.
- To enable investigation of Nm invasion, barrier destruction, and immune responses in a human-relevant context.
Main Methods:
- Derivation of brain-like endothelial cells from human induced pluripotent stem cells (iPSCs).
- Preparation of Neisseria meningitidis (Nm) for infection assays.
- Establishment of infection protocols using iPSC-BECs to model host-pathogen interactions.
- Sample collection strategies for subsequent analysis of bacterial invasion and cellular responses.
Main Results:
- Successfully derived iPSC-BECs that phenocopy key characteristics of native human BECs.
- Established a protocol for using iPSC-BECs to model Nm infection and study host-pathogen dynamics.
- Demonstrated the utility of iPSC-BECs for examining bacterial interaction with the blood-brain barrier.
Conclusions:
- iPSC-BECs offer a robust, human-relevant in vitro model for studying meningococcal meningitis pathogenesis.
- This model facilitates research into Nm invasion mechanisms and host responses at the blood-brain barrier.
- The presented methodology enables further investigation of Nm-BEC interactions and potential therapeutic targets.
