Single-Cell Landscape of Bronchoalveolar Lavage Fluid Identifies Specific Neutrophils during Septic Immunosuppression.

Summary

Single-cell RNA sequencing of BALF from patients with immunosuppressive sepsis delineated a neutrophil-driven immunosuppressive program in the lung. Immunosuppressive genes were upregulated across immune cells, yet only neutrophils expanded markedly in BALF during the immunosuppressive phase. Five neutrophil subpopulations were identified, highlighting neutrophil heterogeneity as a key determinant of pulmonary immune paralysis.

Key Findings

• Single-cell RNA-seq of BALF mapped the immune landscape in immunosuppressive sepsis and revealed a neutrophil-driven immunosuppressive program.
• Immunosuppressive genes were upregulated across immune cells, but only neutrophils markedly increased in BALF during the immunosuppressive phase.
• Five distinct neutrophil subpopulations were identified in BALF of patients with immunosuppressive sepsis.

Clinical Implications

Not practice-changing yet, but supports monitoring and potential targeting of specific neutrophil subsets (e.g., CXCR2-associated populations) to mitigate pulmonary immunosuppression and secondary infections.

Limitations

• Sample size and patient demographics are not specified in the abstract
• Functional validation and longitudinal outcome correlations are not detailed

Future Directions

Validate neutrophil subpopulations across larger, multicenter cohorts; integrate functional assays and spatial profiling; test targeted modulation (e.g., chemokine receptor pathways) and link to clinical outcomes.