Myeloid-Derived Suppressor Cells in Sepsis: Pathophysiology, Duality, and Therapeutic Frontiers.

Sepsis-induced immunosuppression, one of the factors contributing to mortality, is closely mediated by myeloid-derived suppressor cells (MDSCs). This review first outlines MDSC biology, describing their origin from pathological emergency myelopoiesis and classification into polymorphonuclear and monocytic subsets. We then discuss their dual role: an early, protective modulation of cytokine storm that later evolves into harmful immunosuppression associated with secondary infections and death. The underlying mechanisms involve L-arginine depletion ( via arginase 1/inducible nitric oxide synthase), oxidative stress (reactive oxygen species), and induction of regulatory T cells. Therapeutic strategies are summarized, including interventions targeting MDSC differentiation (e.g., all-trans retinoic acid), metabolism (e.g., fatty acid oxidation inhibitors), precision depletion (e.g., anti-LOX-1), and microbiome modulation. Finally, we address challenges to clinical translation-phenotypic heterogeneity, metabolic ambiguity, and the "double-edged sword" of MDSC targeting. Deeper insights into MDSC biology may help develop strategies to improve outcomes in this severe syndrome.