Meningococcal meningitis is a severe infection of the central nervous system that occurs when the pathogen Neisseria meningitidis (Nm) invades the brain endothelial cells (BECs) of the meningeal blood-liquor barrier. The human specificity of Nm and the lack of robust BEC phenotypes in currently used models highlight the need for new models with properties more consistent with BECs in vivo. Here, the researchers demonstrate the utility of iPSC-BECs in vitro to study Nm infection. In addition, host expression patterns in response to Nm infection were profiled by selecting specifically infected iPSC-BECs and sequencing their transcriptome. Overall, this model provides new insights into Nm pathogenesis, including the effects of Nm on barrier properties and tight junction complexes, and suggests that the paracellular pathway may contribute to the traversal of BECs by Nm.
Induced pluripotent stem cell-derived brain endothelial cells as a cellular model to study Neisseria meningitidis infection
Antje Appelt-Menzel(1), Alexandra Schubert-Unkmeir(2), Brandon J. Kim(2)
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