Identifying the anti-infection NK and T cell subgroups in preterm newborns with sepsis using single-cell RNA-seq analysis.

backgroundPreterm infants have the highest incidence of late-onset sepsis, which could result in life-long morbidity, neurodevelopmental disability, and even death. We aimed to explore the anti-infection role of immune cells in treating preterm sepsis.

methodsThe single-cell RNA-seq (scRNA-seq) data of preterm newborns with late-onset sepsis were collected from the Gene Expression Omnibus database. The Seurat and harmony R package were used to perform the scRNA-seq analysis. Gene set enrichment analysis (GSEA) was conducted using the GSVA R package. FindAllMarkers and DAVID databases were used for differentially expressed genes (DEGs) analysis and function annotation of the genes, respectively. Transcriptional regulons analysis was performed applying the SCENIC tool.

resultsWe identified 8 cell clusters, among which the immune cells including the neutrophils, T helper, and NK cells distributed more in the sepsis samples. The immune activity of neutrophils was inhibited with less anti-inflammatory pathway activation. T cells and NK cells exhibited greater activation of immune and detoxification pathways, such as antimicrobial humoral immune response and cellular oxidant detoxification, which contributed to anti-infection response. GZMA + Cytotoxic T cells 2, GRASP + T cells, TMEM107 + NK cells, and GPR171 NK cells have a potential impact on promoting the immune response in preterm infant sepsis, and their key regulons including CREM, EST1, HSPA5, and STAT1 may be potential molecular targets for improving the sepsis treatment.

conclusionThe scRNA-seq analysis of preterm infants with late-onset sepsis revealed enrichment of T and NK cell subsets with heightened regulon activity and antibacterial/oxidative stress programs, indicating potential association with the host infection response.