Alterations of dendritic cells in sepsis: featured role in immunoparalysis

Abstract

Sepsis, the leading cause of mortality in intensive care unit, is characterized by hyperinflammatory response in the early stage and followed by a period of immunosuppression. This immune disorder is believed to be the potent factor that is tightly associated with high mortality in sepsis. Dendritic cells (DCs) serve as professional antigen-presenting cells that play a vital role in immune response by activating T lymphocytes. During the progression of sepsis, DCs have been reported to take part in the aberrant immune response and be necessary for survival. Therefore, a better understanding of the DCs pathology will be undoubtedly beneficial for resolving the problems occurring in sepsis. This review discusses effects of sepsis on DCs number and function, including surface molecules expression, cytokines secretion, and T cell activation, and the underlying mechanism as well as some potential therapeutic strategies.

Figure 1

The changes of DCs during sepsis. When suffering from sepsis, DCs will be lost resulting from apoptosis, but differentiation from monocytes is accelerated. The surface molecules associated with DCs function are changed. At the same time, DCs have an aberrant cytokine secretion which results in immune tolerance status. The potential mechanism may be associated with apoptosis, PPARs, Wnt signal, and epigenetic regulation. MHCII: major histocompatibility complex class II, Ag: antigen, TCR: T cell receptor, PD-1: programmed cell death-1, PD-L1: programmed cell death ligand 1, BTLA: B and T lymphocyte attenuator, and PPARs: peroxisome proliferator-activated receptors.