Key Genes Associated With Functional Specialization of Neonatal Peripheral Monocytes

Purpose: The purpose of this study is to identify genes and transcription factors underlying functional differences in neonatal versus adult peripheral blood monocytes, elucidating mechanisms of severe Group B streptococcus (GBS) infection in neonates. Methods: Differentially expressed genes (DEGs) in neonatal and adult peripheral blood monocytes were detected via RNA sequencing (RNA-seq), followed by assay for transposase-accessible chromatin sequencing (ATAC-seq) to characterize differentially accessible region (DAR)-associated genes. Integrated analyses of RNA-seq and ATAC-seq pinpointed candidate genes and transcription factors. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) validated the mRNA expression of common genes and transcription factors. Results: RNA-seq profiling of neonatal and adult peripheral monocytes identified 669 overexpressed and 440 underexpressed genes in neonates, with overexpressed genes enriched in bacterial response pathways and underexpressed genes in cytokine production and cell killing pathways. Chromatin accessibility analysis revealed 36,782 differential peaks (21,192 gained, 15,590 lost) in neonatal peripheral monocytes. Integrated RNA-seq and ATAC-seq analysis pinpointed 30 overlapping genes among DEGs, DAR-associated genes, and immunologically relevant genes (IRGs). qRT-PCR validated higher expression of CEBPB, JUN, BATF, PTK2B, and ITGAV and lower ADA2 and RORA expression in neonatal peripheral monocytes compared to that in adults. Conclusions: The study revealed distinct differences in the transcriptome and chromatin accessibility between neonatal and adult peripheral monocytes, identifying potential genes linked to GBS infection vulnerability of neonates. These findings advance our understanding of neonatal immune dysfunction in severe GBS disease, informing future therapeutic targets.