Neutrophil Pyroptosis: New Perspectives on Sepsis

Cell Mol Life Sci. 2019 Jun;76(11):2031-2042. doi: 10.1007/s00018-019-03060-1. Epub 2019 Mar 14.

Abstract

Pyroptosis is a caspase-1 or caspase-4/5/11-dependent programmed cell death associated with inflammation, which is initiated by inflammasomes or cytosolic LPS in innate immunity. Sepsis is a life-threatening organ dysfunction caused by an imbalance in the body's response to infection. It is a complex interaction between the pathogen and the host's immune system. Neutrophils play the role of a double-edged sword in sepsis, and a number of studies have previously shown that regulation of neutrophils is the most crucial part of sepsis treatment. Pyroptosis is one of the important forms for neutrophils to function, which is increasingly understood as a host active immune response. There is ample evidence that neutrophil pyroptosis may play an important role in sepsis. In recent years, a breakthrough in pyroptosis research has revealed the main mechanism of pyroptosis. However, the potential value of neutrophil pyroptosis in the treatment of sepsis did not draw enough attention. A literature review was performed on the main mechanism of pyroptosis in sepsis and the potential value of neutrophils pyroptosis in sepsis, which may be suitable targets for sepsis treatment in future.

Keywords: Caspase; IL-18; IL-1β; Inflammasome; Neutrophil; PITs; Pyroptosis; Sepsis.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / therapeutic use
  • Bacterial Infections / drug therapy
  • Bacterial Infections / genetics
  • Bacterial Infections / immunology*
  • Bacterial Infections / pathology
  • CARD Signaling Adaptor Proteins / genetics
  • CARD Signaling Adaptor Proteins / immunology
  • Caspases / genetics
  • Caspases / immunology*
  • Gene Expression Regulation
  • Host-Pathogen Interactions / immunology
  • Humans
  • Immunity, Innate
  • Inflammasomes / drug effects
  • Inflammasomes / immunology*
  • Interleukin-18 / genetics
  • Interleukin-18 / immunology
  • Interleukin-1beta / genetics
  • Interleukin-1beta / immunology
  • Lipopolysaccharides / pharmacology
  • Neutrophils / drug effects
  • Neutrophils / immunology*
  • Neutrophils / microbiology
  • Pyroptosis / drug effects
  • Pyroptosis / immunology*
  • Sepsis / drug therapy
  • Sepsis / genetics
  • Sepsis / immunology*
  • Sepsis / pathology

Substances

  • Anti-Inflammatory Agents
  • CARD Signaling Adaptor Proteins
  • IL1B protein, human
  • Inflammasomes
  • Interleukin-18
  • Interleukin-1beta
  • Lipopolysaccharides
  • interleukin 18 protein, human
  • Caspases