Peripheral Blood Mononuclear Cells in Sepsis: Immune Trajectories, Monocyte Dysfunction, and Translational Biomarkers

Sepsis is characterized by a dynamic and heterogeneous immune response in which hyperinflammation and immunosuppression often coexist and change over time. Peripheral blood mononuclear cells (PBMCs), including monocytes and lymphocyte subsets, provide an accessible window into this evolving immune trajectory and can be repeatedly assessed during disease progression. In this narrative review, we synthesize recent evidence from single-cell and spatial omics, mechanistic studies, and PBMC-based biomarker research, with a focus on three connected themes: time-dependent PBMC remodeling, monocyte/macrophage dysfunction, and translational immune biomarkers. Current evidence indicates that PBMC remodeling in sepsis is marked by monocyte state transitions, HLA-DR downregulation, lymphocyte apoptosis and exhaustion, regulated cell death, and immunometabolic reprogramming. These changes help explain why some patients recover after the acute inflammatory phase, whereas others progress toward persistent immunoparalysis, secondary infection, prolonged critical illness, or poor outcomes. PBMC-derived biomarkers, including transcriptomic signatures, monocyte phenotypes, lymphocyte exhaustion markers, metabolic indicators, and functional immune assays, may improve immune phenotyping and risk stratification. However, clinical translation remains limited by cohort heterogeneity, age-related differences, timing-dependent immune states, assay standardization, and insufficient prospective validation. Future studies should prioritize longitudinal, age-stratified, and biomarker-guided designs to determine whether PBMC-based immune monitoring can support individualized immunomodulatory strategies in sepsis.