Sepsis-associated immunosuppression: mechanistic Insights, Biomarkers, and therapeutic perspectives

Sepsis is recognized as a major global health concern, characterized by a dysregulated and uncontrolled host response to infection that results in organ dysfunction and high mortality. Clinically, the course of sepsis typically begins with an intense hyperinflammatory phase, which is often followed by an immunosuppressive stage in many patients. This immunosuppressive state significantly increases susceptibility to secondary infections, complicates treatment, and worsens overall survival. The immunopathogenesis of sepsis-associated immune dysfunction involves profound alterations in immune cells, particularly monocytes, macrophages, and T lymphocytes. In addition, metabolic reprogramming through signaling pathways such as mTOR, AMPK, and PI3K-Akt contributes to the imbalance of immune responses and the deepening of immunosuppression. Currently, biomarkers such as HLA-DR expression are employed to monitor immune status and to predict clinical outcomes in septic patients. From a therapeutic perspective, the use of immunostimulatory agents, biomarker-guided monitoring, and personalized immunomodulatory strategies has gained increasing attention. Recent clinical and experimental findings suggest that these approaches may help restore immune competence and improve patient outcomes. The aim of this review is to provide a comprehensive synthesis of current knowledge regarding the cellular, molecular, and metabolic mechanisms underlying sepsis-associated immunosuppression and to discuss their potential implications for the development of targeted therapeutic strategies.