Abstract
Programmed cell death 1 (PD-1) plays an important pathologic role in sepsis-induced immunosuppression. However, whether PD-1 overexpression occurs early during septic shock is unknown and its regulation mechanism is also unknown. Our study investigated the expressions of PD-1/programmed death-ligand 1 (PD-L1) on immune cells in peripheral blood from the early-stage septic shock patients. We found that both PD-1 and PD-L1 showed increased expressions on the CD4+ T cells and monocytes. It indicated that PD-1 expression might be an early biomarker to assess illness severity and predict the prognosis of septic shock. Then, we further investigated the mechanism underlying the regulation of PD-1 expression. Our data showed that Notch signaling pathway was activated in both septic shock patients and lipopolysaccharide- (LPS-) tolerant THP1 cells and both interleukin-10 (IL-10) and PD-1 were increased in the THP1 cells. Inhibition of Notch signaling by N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenyl glycinet-butyl ester (DAPT) induced significantly decreased expressions of PD-1 and IL-10 in the LPS-tolerant cell model. Our work suggested that Notch signaling pathway was involved in the regulation of PD-1 expression.
Highlights
Sepsis, a systemic inflammatory response to infection, is one of the most challenging clinical problems worldwide and the leading cause of death in noncoronary ICUs [1]
First we investigated the expressions of PD1/programmed death-ligand 1 (PD-L1) on both CD4+ T cells and monocytes from peripheral blood in the early-stage septic shock patients and showed the relationship between Programmed cell death 1 (PD-1)/PD-L1 and clinical outcomes
Patients with septic shock showed increased numbers of white blood cells compared to healthy volunteers. 29 septic shock patients were infected with Gram-negative bacilli, 22 patients were infected with Gram-positive cocci, and 5 patients were infected with fungi
Summary
A systemic inflammatory response to infection, is one of the most challenging clinical problems worldwide and the leading cause of death in noncoronary ICUs [1]. Patients in the immunosuppressive phase of sepsis are often unable to control the primary infection and may acquire a secondary infection during hospitalization This phenomenon has recently been identified as an important cause of mortality during sepsis [3]. Tregs are involved in the regulation of peripheral tolerance which demonstrated again that immunosuppression was a key factor in the development of sepsis [5, 6]. All these suggested that understanding the mechanism underlying the immunosuppression will help to identify the novel targets in the treatment of sepsis
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