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

Summary

Single-cell profiling reveals that specific monocyte subsets (Mono1/Mono4) in PICS exhibit immunosuppressive and pro-apoptotic interactions with B and CD8 T cells. PICS features reduced naive/memory B cells, expanded plasma cells, prognostically favorable active memory B/IGHA1 plasma cell signatures, dysfunctional proliferative CD8TEMRA in deaths, and proliferative megakaryocytes; key findings were validated in murine models.

Key Findings

• Monocyte subsets Mono1/Mono4 show immunosuppressive and pro-apoptotic effects on B and CD8 T cells in PICS.
• PICS exhibits reduced naive/memory B cells, expanded plasma cells, and a more active antigen-processing signature in B cells than sepsis.
• Better PICS prognosis associates with active memory B cells and IGHA1 plasma cells; deaths show proliferative, dysfunctional CD8TEMRA.
• Megakaryocyte proliferation and immunomodulatory changes are prominent in PICS and validated in murine models.

Clinical Implications

Immune-cell signatures (e.g., active memory B/IGHA1 plasma cells vs. dysfunctional CD8TEMRA) may enable risk stratification and inform targeted immunomodulatory strategies in post-sepsis patients.

Limitations

• Observational design limits causal inference
• Sample size and external generalizability are not detailed in the abstract

Future Directions

Prospective validation of prognostic immune signatures, interventional trials targeting identified pathways (e.g., CD8TEMRA dysfunction, B-cell programs), and integration with clinical risk scores.