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

BACKGROUND: Management of persistent inflammation, immunosuppression, and catabolism syndrome (PICS) after sepsis remains challenging for patients in the intensive care unit, experiencing poor quality of life and death. However, immune-cell signatures in patients with PICS after sepsis remain unclear. METHODS: We determined immune-cell signatures of PICS after sepsis at single-cell resolution. Murine cecal ligation and puncture models of PICS were applied for validation. FINDINGS: Immune functions of two enriched monocyte subpopulations, Mono1 and Mono4, were suppressed substantially in patients with sepsis and were partially restored in patients with PICS after sepsis and exhibited immunosuppressive and pro-apoptotic effects on B and CD8T cells. Patients with PICS and sepsis had reduced naive and memory B cells and proliferated plasma cells. Besides, naive and memory B cells in patients with PICS showed an active antigen processing and presentation gene signature compared to those with sepsis. PICS patients with better prognoses exhibited more active memory B cells and IGHA1-plasma cells. CD8TEMRA displayed signs of proliferation and immune dysfunction in the PICS-death group in contrast with the PICS-alive group. Megakaryocytes proliferation was more pronounced in patients with PICS and sepsis than in healthy controls, with notable changes in the anti-inflammatory and immunomodulatory effects observed in patients with PICS and verified in mice models. CONCLUSIONS: Our study evaluated PICS after sepsis at the single-cell level, identifying the heterogeneity present within immune-cell subsets, facilitating the prediction of disease progression and the development of effective intervention. FUNDING: This work was supported by the National Natural Science Foundation of China, Shanghai Municipal Health Commission "Yiyuan New Star" Youth Medical Talent Cultivating Program, and Shanghai Clinical Research Center for Anesthesiology.