Early Expansion of Monocytic Myeloid-Derived Suppressor Cells Predicts Survival in Sepsis and Is Possibly Associated
Juanli Liu1,2, Tana Wuren1, Xiaoyan Song1
1Research Center for High Altitude Medicine, Key Laboratory of High Altitude Medicine (Ministry of Education), Key Laboratory of Application and Foundation for High Altitude Medicine Research in Qinghai Province (Qinghai-Utah Joint Research Key Laboratory for High Altitude Medicine), Qinghai University, 81000 Xining, Qinghai, China.
Background:
Sepsis is characterized by profound immune dysregulation, in which myeloid-derived suppressor cells (MDSCs) serve as key regulators of the host immune response. However, the prognostic significance of distinct MDSC subsets during the early phase of sepsis remains incompletely understood.
Methods:
In this prospective cohort study, flow cytometry was used to quantify circulating MDSC subsets in sepsis patients within 24 hours of intensive care unit (ICU) admission and in healthy control subjects. Patients were followed to establish 90-day survival, and the prognostic significance of MDSC subset frequencies on admission was evaluated using receiver operating characteristic (ROC) curve analysis and Cox regression models. Multivariate Cox models were adjusted for disease severity scores. A murine cecal ligation and puncture (CLP) model of sepsis was also used to investigate temporal and tissue-specific MDSC dynamics and to examine endoplasmic reticulum (ER) stress-related signaling within these cells.
Results:
Compared with healthy controls, patients with sepsis exhibited the marked expansion of circulating MDSCs, including both polymorphonuclear and monocytic subsets. Among these, the proportion of circulating monocytic MDSCs (M-MDSCs) on ICU admission was significantly higher in 90-day survivors than in non-survivors. After adjusting for disease severity and other clinical variables, higher M-MDSC frequencies were independently associated with lower 90-day mortality. ROC curves confirmed the ability of the M-MDSC proportion to predict 90-day mortality. In the CLP model, MDSC subsets displayed temporal and tissue-specific dynamics that differed between the acute and recovery phases of sepsis. MDSCs isolated from septic mice exhibited ER stress-related pathway activation in the spleen and bone marrow. Collectively, these findings suggest that early M-MDSC expansion represents a distinct immunological phenotype associated with favorable outcomes in sepsis.
Conclusions:
An early increase in circulating M-MDSCs is associated with improved 90-day survival in patients with sepsis. These findings underscore the dynamic, context-dependent role of M-MDSCs in sepsis, indicating that early immunoregulatory responses, possibly associated with activation of ER stress pathways, may represent an adaptive mechanism leading to favorable clinical outcomes.