Multi-omics single-cell atlas reveals kidney-infiltrating S100A8/A9-high neutrophils as pioneer cells driving fatal urosepsis

Urosepsis is a critical complication with up to 20-30% of cases progressing to septic shock and mortality, yet the tissue-specific immune landscape and cellular dynamics during urosepsis progression remain poorly understood. While recent studies have characterized peripheral blood immune cell states in sepsis, comprehensive analysis of temporal changes in tissue-resident immune cells during fatal sepsis progression is notably absent, particularly in the context of urosepsis. The role of distinct neutrophil subtypes in organ damage and the molecular mechanisms driving urosepsis pathogenesis require further elucidation. To address this critical knowledge gap, we performed comprehensive multi-omics analysis including bulk RNA sequencing on 12 rat kidney samples and single-cell RNA sequencing on kidney tissues from 20 rats across different disease stages using a novel Sepsis-Related Death (SRD) rat model, providing the first comprehensive single-cell atlas of kidney tissue during urosepsis progression and revealing novel pathogenic mechanisms for therapeutic intervention.