Interaction between microglia and endothelial cell facilitates inflammatory BBB disruption in bacterial meningitis

The blood-brain barrier (BBB) serves as a physiological and functional protective barrier between the brain parenchyma and the peripheral circulatory system, which protects the brain from bloodborne agents, including pathogens and toxins. Bacterial meningitis, a devastating disease occurring worldwide, remains a major cause of high mortality and morbidity, which can trigger BBB disruption and intense intracerebral inflammatory responses. Using single-cell RNA sequencing (scRNA-seq), we show that during neonatal meningitis Escherichia coli (NMEC) challenges, brain endothelial cells undergo pyroptosis and trigger the pyroptotic cascade through intercellular interactions, leading to inflammatory disruption of BBB and strong immune response within the brain. Analyses of the scRNA-seq dataset demonstrate that brian endothelial cells and microglia display the most sensitive to bacterial responses, and the crosstalk between brain vascular cells and immune cells remodels the central nervous system immune microenvironment. We employed a single-cell sequencing approach using 10x Genomics scRNAseq to study neonatal meningitis caused by Escherichia coli (NMEC) infection in mice. This study reveals that NMEC triggers pyroptosis in cerebral cortex cells, leading to inflammatory disruption of the BBB, activation of the apoptotic cascade, and triggering a strong immune response within the brain, disrupting the central nervous system's immune microenvironment. It helps us understand the immunopathological mechanisms of NMEC-induced meningitis and provides a theoretical basis for developing innovative therapeutic strategies targeting the function regulation of cortical cells or microglia and the apoptotic process, thus opening up new avenues for the prevention and treatment of neonatal meningitis.