Abstract
Background: Myeloid derived suppressor cells (MDSCs) have been reported to keep elevating during sepsis. The current study was performed to investigate the immunosuppressive effect of MDSCs and their subsets with the underlying mechanisms.Methods: The immunosuppressive status was manifested by the apoptosis of splenocytes, quantity of T cells and PD-1 expression. The dynamics of quantity and PD-L1 level of MDSCs and the subsets were determined over time. The subset of MDSCs with high PD-L1 level was co-cultured with T cells to observe the suppressive effect.Results: Abdominal abscess was observed after 7 days post-sepsis. Five biomarkers related to organ functions were all significantly higher in the CLP group. The survival rate was consistent with the middle grade severity of sepsis model. Apoptosis of splenocytes increased over time during sepsis; CD4 + T cell decreased from day 1 post-sepsis; CD8+ T cells significantly reduced at day 7. The PD-1 expression in spleen was upregulated from an early stage of sepsis, and negatively related with the quantity of T cells. MDSCs were low at day 1 post-sepsis, but increased to a high level later; the dynamics of PMN-MDSC was similar to MDSCs. PD-L1 on MDSCs was highest at day 1 post-sepsis; PMN-MDSC was the main subset expressing PD-L1. The PMN-MDSC with high PD-L1 expression level extracted on day 1 after surgery from CLP mice significantly inhibited the proliferation of T cells.Conclusions: Sepsis-induced immunosuppression is initiated from a very early stage, a high expression level of PD-L1 on MDSCs and the main subset, PMN-MDSC might play a critical role suppressive role on T cells through PD-L1/PD-1 axis.
Highlights
Sepsis is a heterogeneous syndrome that develops as a dysregulated host response to an infection, and is associated with acute organ dysfunction which represents a high risk of death [1]
The aim of the current study is to figure out how and when Myeloid derived suppressor cells (MDSCs) exert the suppressive role during sepsis, which subset is the main immunosuppressive group and whether PD-L1/PD-1 axis is involved in the immunosuppressive function of sepsisinduced MDSCs in a classic cecal ligation and puncture (CLP)-induced sepsis mouse model
The present study demonstrated that PD-1 was upregulated on spleen CD4+ T cells and CD8+ T cells during sepsis, which represented the immunosuppressive state of CLP mice
Summary
Sepsis is a heterogeneous syndrome that develops as a dysregulated host response to an infection, and is associated with acute organ dysfunction which represents a high risk of death [1]. MDSCs in Sepsis-Induced Immune Suppression diagnosis, fluid resuscitation, timely delivery of antibiotics and other improvements in supportive care for critically ill patients, such as lung protective ventilation and judicious use of blood products, have distinctly improved the survival rate of sepsis at an early stage, uncontrolled primary and secondary infection resulting from sepsis-induced dysregulation of immune system may be the main cause of mortality in septic patients [5]. Sepsis induced immunosuppression is characterized by lymphopenia and loss of immune function resulting from a loss of B cells and T cells via apoptosis [7]. A subsequent study reported that sepsis enhanced expression of PD-1 on peripheral T cells and programmed cell death 1 ligand (PD-L1 or CD274) on spleen B cells and monocytes in a cecal ligation and puncture (CLP) model [13]. The current study was performed to investigate the immunosuppressive effect of MDSCs and their subsets with the underlying mechanisms
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