Myeloid-Derived Suppressor Cells in Sepsis

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.

Keywords: biomarker; immunosuppression; infectious disease; inflammation; innate immunity; myeloid-derived suppressor cells; personalized medicine; sepsis.

Figure 1

MDSCs in sepsis. (A) Factors generated during sepsis induce the expansion and egress of MDSCs from the bone marrow into the peripheral blood. (B) Main signaling pathways involved in the expansion and the immunosuppressive functions of MDSCs during sepsis. (C) Biological functions of MDSCs during sepsis. See body text for detailed explanations. DAMPs, danger-associated molecular patterns; MAMPs, microbial-associated molecular patterns; IL-6R^*, interleukin (IL)-6 receptor family of cytokines (commonly referred to as gp130 cytokines); gp130, glycoprotein 130; TLRs, toll-like receptors; IL-1R, interleukin-1 receptor; MyD88, Myeloid differentiation primary response 88; NF-κB, nuclear factor-κB; NFI-A, nuclear factor I A; STAT, signal transducer and activator of transcription; miR, microRNA; Mφ, macrophage; DC, dendritic cell; Th, T helper; NK, natural killer; Treg, T regulatory; IFNγ, interferon γ; ROS, reactive oxygen species; RNS, reactive nitrogen species; TGF-β, transforming growth factor-β; IL-10, interleukin-10.