Abstract
Streptococcus pneumoniae, a Gram-positive, human-specific commensal infectious pathogen, poses a significant global health threat, especially in children under five, often resulting in fatalities. The intricacies of the immune response in pneumococcal meningitis (PM) remain elusive, necessitating a meticulous examination of immune cell subsets at the single-cell resolution. In this study, we performed single-cell RNA sequencing of peripheral blood mononuclear cells from PM patients and healthy individuals. We found significant relative changes in the compositions of immune cell subset, with significant relative increases in platelets, neutrophils, and their precursors, alongside relative decreases in natural killer (NK) cells, T cell subtypes, and plasmacytoid dendritic cells in PM patients. Functional enrichment analyses revealed an up-regulation of neutrophils-related immune genes across multiple immune cell types, including platelets, myeloid cells and B cells, suggesting excessive neutrophil activation. However, a down-regulation of genes involved in antigen processing and presentation in myeloid cells and B cells in the PM group indicated a relative dampening of the adaptive immune response in the PM patients. This was further corroborated by the reduced proportions of plasmacytoid dendritic cells and T cells. Furthermore, genes involved in cytotoxity were down-regulated in both NK cells and T cells, alongside impaired T cell activation. Notably, distinct B cell subtypes, including unique naïve B cell clusters, demonstrated differentially expressed genes associated with both innate and adaptive immune responses. In conclusion, our study provides a comprehensive single-cell transcriptomic landscape of immune responses in PM. The identified cellular and molecular signatures offer potential targets for therapeutic intervention and provide a foundation for further investigation into the immunopathogenesis of pneumococcal meningitis.