The “Self-Sacrifice” of ImmuneCells in Sepsis

Abstract

Sepsis is a life-threatening organ dysfunction caused by the host’s malfunctioning response to infection. Due to its high mortality rate and medical cost, sepsis remains one of the world’s most intractable diseases. In the early stage of sepsis, the over-activated immune system and a cascade of inflammation are usually accompanied by immunosuppression. The core pathogenesis of sepsis is the maladjustment of the host’s innate and adaptive immune response. Many immune cells are involved in this process, including neutrophils, mononuclear/macrophages and lymphocytes. The immune cells recognize pathogens, devour pathogens and release cytokines to recruit or activate other cells in direct or indirect manner. Pyroptosis, immune cell-extracellular traps formation and autophagy are several novel forms of cell death that are different from apoptosis, which play essential roles in the progress of sepsis. Immune cells can initiate “self-sacrifice” through the above three forms of cell death to protect or kill pathogens. However, the exact roles and mechanisms of the self-sacrifice in the immune cells in sepsis are not fully elucidated. This paper mainly analyzes the self-sacrifice of several representative immune cells in the forms of pyroptosis, immune cell-extracellular traps formation and autophagy to reveal the specific roles they play in the occurrence and progression of sepsis, also to provide inspiration and references for further investigation of the roles and mechanisms of self-sacrifice of immune cells in the sepsis in the future, meanwhile, through this work, we hope to bring inspiration to clinical work.

Dysregulation of neutrophil death in sepsis

“…Although the mechanism of neutrophil cell death in sepsis remains to be investigated, and the drug intervention targeting at neutrophil death is even rare, there is evidence that neutrophils with dysregulated death types are more harmful than protective ( 132 ). Targeting at neutrophil cell death may be a promising treatment against sepsis.…”

“…In addition to their beneficial effects against foreign invasion, NETs also have a number of deleterious implications on host tissues during sepsis ( 43 , 131 , 132 ). In sepsis, endothelial cell (EC) activation is viewed as an important part, in which NETs and their components play an important role ( 132 ).…”

“…In addition to their beneficial effects against foreign invasion, NETs also have a number of deleterious implications on host tissues during sepsis ( 43 , 131 , 132 ). In sepsis, endothelial cell (EC) activation is viewed as an important part, in which NETs and their components play an important role ( 132 ). NETs can synergize with IL-1α and cathepsin G to facilitate the activation of ECs and enhance the formation of thrombosis, which may amplify and spread the thrombus related EC dysfunction caused by epidermal erosion ( 133 ).…”

Sepsis-Induced Brain Dysfunction: Pathogenesis, Diagnosis, and Treatment

“…In a word, pyrotosis maybe a reason and a potential therapeutic target for multiple organ dysfunction in sepsis [ 15 ]. All immune cells of the innate immune system are mobilized to participate in the process of sepsis [ 20 ]. Neutrophils migrate to the inflammation site, where they perform anti-inflammation and eliminate pathogens [ 20 ].…”

“…All immune cells of the innate immune system are mobilized to participate in the process of sepsis [ 20 ]. Neutrophils migrate to the inflammation site, where they perform anti-inflammation and eliminate pathogens [ 20 ]. The activated mononuclear/macrophage cells phagocytose, kill pathogens, and present antigens [ 21 ].…”