Single-cell analysis identifies a type I interferon-associated neutrophil signature in bacterial meningitis

Bacterial meningitis (BM) is a central nervous system infection characterized by high mortality and disability rates. Neutrophils, as the first-line innate immune cells in host defense against bacterial invasion, play a crucial role in the pathogenesis of this disease. However, the transcriptomic characteristics of neutrophils in BM remain poorly defined, limiting our understanding of the underlying mechanisms. In this study, we analyzed single-cell RNA sequencing (scRNA-seq) data from the public database GSE221681 to map the transcriptomic landscape of meningeal immune cells in a mouse model of BM, with a focus on analyzing transcriptional changes in neutrophils under homeostatic and disease conditions. Our analysis constructed a single-cell transcriptomic atlas of meningeal immune cells in BM mice and identified seven major cell clusters. Neutrophils exhibited transcriptional changes in the disease state, marked by elevated expression of interferon-stimulated genes (ISGs) and downregulation of metabolic gene programs. CellChat analysis predicted that neutrophils may exhibit enhanced communication capacity both as signal senders and receivers during disease, potentially interacting with other immune cells via chemokine-mediated pathways. We then established a mouse model of meningoencephalitis and observed increased type I interferon gene expression (Ifna/Ifnb) in bulk brain tissue by qPCR. In conclusion, during acute pneumococcal meningitis, neutrophils exhibit a transcriptional signature characterized by the upregulation of ISGs and are predicted to participate in meningeal immune networks.