Abstract
Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells characterized by their immunosuppressive functions. MDSCs expand during chronic and acute inflammatory conditions, the best described being cancer. Recent studies uncovered an important role of MDSCs in the pathogenesis of infectious diseases along with sepsis. Here we discuss the mechanisms underlying the expansion and immunosuppressive functions of MDSCs, and the results of preclinical and clinical studies linking MDSCs to sepsis pathogenesis. Strikingly, all clinical studies to date suggest that high proportions of blood MDSCs are associated with clinical worsening, the incidence of nosocomial infections and/or mortality. Hence, MDSCs are attractive biomarkers and therapeutic targets for sepsis, especially because these cells are barely detectable in healthy subjects. Blocking MDSC-mediated immunosuppression and trafficking or depleting MDSCs might all improve sepsis outcome. While some key aspects of MDSCs biology need in depth investigations, exploring these avenues may participate to pave the way toward the implementation of personalized medicine and precision immunotherapy for patients suffering from sepsis.
Highlights
Sepsis is one of the leading causes of preventable death
We summarize and discuss our current knowledge about the role played by Myeloid-derived suppressor cells (MDSCs) during sepsis and the potential of using MDSCs as biomarkers and therapeutic targets of sepsis
MDSCs play a dual role during infection and sepsis
Summary
Sepsis is one of the leading causes of preventable death. Sepsis is defined as a “life-threatening organ dysfunction caused by a dysregulated host response to infection” [1]. As observed in sepsis, stimulates the egress of immature myeloid cells from the bone marrow into the blood stream and the gain immunosuppressive functions [26, 44] (Figure 1). A meta-analysis of ten Korean and one Egyptian studies including 1,822 sepsis patients suggests that an elevated DNI (i.e., an increased proportion of immature granulocytes) is associated with mortality [100].
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