Comprehensive single-cell analysis reveals novel anergic antigen-presenting cell subtypes in human sepsis

Background Sepsis is a life-threatening condition with high mortality. A few studies have emerged utilizing single-cell RNA sequencing (scRNA-seq) to analyze gene expression at the resolution in sepsis, but comprehensive high-resolution analysis of blood antigen-presenting cells has not been conducted. Methods All published human scRNA-seq data were downloaded from single cell portal database. After manually curating dataset, we extracted all cells, including dendritic (DCs) and monocytes, for identification subpopulations their profiling intercellular interactions between septic patients healthy controls. Finally, further validated findings by performing deconvolution on bulk (RNA-seq) flow cytometry. Results Within traditional DC populations, discovered novel anergic subtypes characterized low major histocompatibility complex class II expression. Notably, these showed significant increase patients. Additionally, found that previously reported immunosuppressive monocyte subtype, Mono1, exhibited similar profile DCs. The consistency our was confirmed through validation using RNA-seq cytometry, ensuring accurate patterns. Conclusions This study represents first revealing disease-associated subtypes. These provide new insights into cellular mechanisms immune dysregulation bacterial sepsis.