Contribution of Dendritic Cell Responses to Sepsis-Induced Immunosuppression and to Susceptibility to Secondary Pneumonia

Abstract

Dendritic cells (DCs) are bone marrow derived cells which continuously seed in peripheral tissue. During infection, DCs play an essential interface between innate and adaptive immunity. Pneumonia is a lung inflammation triggered by pathogens and is characterized by excessive release of inflammatory cytokines that activate innate and acquired immunity. Pneumonia induces a rapid and protracted state of susceptibility to secondary infection, a state so-called sepsis-induced immunosuppression. In this review, we focus on the role of DCs in the development of this state of immunosuppression. Early during inflammation, activated DCs are characterized by decreased capacity of antigen (cross)- presentation of newly encountered antigens and decreased production of immunogenic cytokines, and sepsis-induced immunosuppression is mainly explained by a depletion of immature DCs which had all become mature. At a later stage, newly formed respiratory immature DCs are locally programmed by an immunological scare left-over by inflammation to induce tolerance. Tolerogenic Blimp1+ DCs produce suppressive cytokines such as tumor growth factor-B and participate to the maintenance of a local tolerogenic environment notably characterized by accumulation of Treg cells. In mice, the restoration of the immunogenic functions of DCs restores the mucosal immune response to pathogens. In humans, the modulation of inflammation by glucocorticoid during sepsis or trauma preserves DC immunogenic functions and is associated with resistance to secondary pneumonia. Finally, we propose that the alterations of DCs during and after inflammation can be used as biomarkers of susceptibility to secondary pneumonia and are promising therapeutic targets to enhance outcomes of patients with secondary pneumonia.

Sestrin2 protects dendritic cells against endoplasmic reticulum stress-related apoptosis induced by high mobility group box-1 protein

“…DCs are critical potent antigen-presenting cells that are key factors in immune response by initiating T lymphocytes. Previous studies indicated that the decreased number of splenic DCs in mice suffered from sepsis and blood DCs in septic patients played important roles in sepsis-induced immune paralysis 28,29 . The loss of DCs during sepsis appears to be a universal phenomenon, and it acts as a mark of immune depression.…”

Parenteral supplementation of omega-3 fatty acid on the prognosis of sepsis: a real world retrospective study

“…The immunosuppression induced by sepsis is mainly due to the depletion of mature immature dendritic cells. However, the late development of immune tolerance can lead to the release of tumor necrosis factor inhibitory cytokines by DCs, which is involved in maintaining the local tolerance environment characterized by Treg cell aggregation [14]. By targeting DCs, it is found that the loss of DC quantity and function caused by sepsis is one of the reasons for the de ciency of CD8 T cell immune function, and the treatment of improving the state of DCs after sepsis may be helpful to the recovery of immune function of CD8+ T cell [15].…”

Parenteral supplementation of omega-3 fatty acid on the prognosis of sepsis: a retrospective study

“…The immunosuppression induced by sepsis is mainly due to the depletion of mature immature dendritic cells. However, the late development of immune tolerance can lead to the release of tumor necrosis factor inhibitory cytokines by DCs, which is involved in maintaining the local tolerance environment characterized by Treg cell aggregation [14].…”