Single-cell transcriptome profiling of sepsis identifies HLA-DR^lowS100A^high monocytes with immunosuppressive function

Area of Science:

• Immunology
• Cell Biology
• Genomics

Background:

• Sepsis frequently leads to persistent immunosuppression, worsening patient outcomes.
• Significant patient heterogeneity complicates identifying precise indicators of sepsis trajectories and immune changes.

Purpose of the Study:

• To identify specific immune cell markers and their functions in sepsis.
• To explore potential therapeutic targets for sepsis-induced immunosuppression.

Main Methods:

• Cross-species single-cell RNA sequencing (scRNA-seq) of human sepsis patients and a murine sepsis model.
• Flow cytometry, confocal microscopy, and Western blotting to detect S100A9+ monocytes.
• In vitro co-culture assays and in vivo pharmacological inhibition of S100A9.

Main Results:

• Identified a unique monocyte subset (HLA-DR low S100A high) enriched in septic patients, associated with immunosuppression.
• Found a similar monocyte subtype in mice linked to late sepsis and immune compromise.
• Demonstrated that S100A9+ monocytes suppress CD4+ T cell responses, and Paquinimod partially reversed this suppression.

Conclusions:

• HLA-DR low S100A high monocytes are correlated with sepsis-induced immunosuppression.
• Inhibiting S100A9 offers a potential therapeutic strategy to mitigate sepsis-induced immune depression.