Immune-cell signatures of persistent inflammation, immunosuppression, and catabolism syndrome after sepsis.

Summary

Single-cell profiling in sepsis survivors delineates immune-cell states associated with PICS: suppressed monocyte subsets that exert immunosuppressive/pro-apoptotic effects on B and CD8 T cells, reduced naive/memory B cells with antigen presentation signatures in PICS, and prognostically relevant increases in memory B and IGHA1 plasma cells in better outcomes. CD8TEMRA proliferation and dysfunction associate with death; megakaryocyte proliferation and immunomodulation are notable and validated in mice.

Key Findings

• Two monocyte subpopulations (Mono1, Mono4) showed substantial functional suppression in sepsis and partial restoration in PICS, exerting immunosuppressive and pro-apoptotic effects on B and CD8 T cells.
• Naive and memory B cells were reduced in sepsis and PICS; in PICS, these B cells exhibited active antigen processing/presentation signatures, with better prognosis linked to more active memory B cells and IGHA1 plasma cells.
• CD8TEMRA proliferation and immune dysfunction associated with death in PICS; megakaryocyte proliferation and immunomodulatory changes were prominent and validated in murine PICS models.

Clinical Implications

Supports development of immune monitoring panels (e.g., monocyte subsets, memory B/IGHA1 plasma cell abundance, CD8TEMRA states) to stratify PICS risk and tailor immunotherapies or rehabilitation strategies.

Limitations

• Observational design limits causal inference regarding immune-cell states and outcomes
• Cohort size and center details are not specified in the abstract; external validation in diverse populations is needed

Future Directions

Translate signatures into clinically deployable biomarkers and test targeted immunomodulation strategies in PICS-informed trials.