Abstract
Bacterial meningitis (BM) requires rapid intervention, especially in immunocompromised populations. Understanding early immune responses is crucial, as they precede clinical symptoms; however, comprehensive studies remain limited. This research investigates immune-related genes to improve BM diagnosis and treatment. Mendelian randomization, differential gene expression analysis, and co-expression network analysis identified key genes associated with BM. Immune cell ratio calculations and infiltration analyses demonstrated altered immune cell proportions. Spearman correlation analysis revealed relationships between gene expression and immune cell types. Single-cell RNA sequencing, gene set enrichment analysis, and pseudotime analysis explored changes in gene expression and cell proportions across disease stages, focusing on the roles of key genes in specific immune cells. Ring Finger Protein 144B (RNF144B) was identified as a risk gene predominantly expressed in monocytes and neutrophils. Conversely, FYN Proto-Oncogene (FYN) was identified as a protective gene primarily associated with NKT cells. During BM onset, increased RNF144B expression positively correlated with elevated neutrophil levels, while reduced FYN expression correlated with decreased NKT cell levels. During remission and recovery, RNF144B expression and neutrophil proportions decreased, whereas FYN expression and NKT cell proportions increased. NKT cells appeared to play a protective role, with FYN potentially modulating T-cell receptor function in these cells, thereby reducing BM risk. RNF144B and FYN expression exhibit opposing trends in peripheral blood across BM stages, suggesting their potential as biomarkers for diagnosis and monitoring. These findings provide a valuable reference for early intervention strategies and personalized treatment approaches tailored to specific disease stages in the clinic.