The Role of Autophagy in Sepsis: Protection and Injury to Organs

Abstract

Sepsis is a systemic inflammatory disease with infection, and autophagy has been shown to play an important role in sepsis. This review summarizes the main regulatory mechanisms of autophagy in sepsis and its latest research. Recent studies have shown that autophagy can regulate innate immune processes and acquired immune processes, and the regulation of autophagy in different immune cells is different. Mitophagy can select damaged mitochondria and remove it to deal with oxidative stress damage. The process of mitophagy is regulated by other factors. Non-coding RNA is also an important factor in the regulation of autophagy. In addition, more and more studies in recent years have shown that autophagy plays different roles in different organs. It tends to be protective in the lungs, heart, kidneys, and brain, and tends to be damaging in skeletal muscle. We also mentioned that some drugs can regulate autophagy. The process of modulating autophagy through drug intervention appears to be a new potential hope for the treatment of sepsis.

Keywords: autophagy; immunity; ncRNAs; oxidative stress; sepsis.

Figure 1

Autophagy regulation mechanism of different immune cells in sepsis. An overview of many possible mechanisms in innate immune and acquired immune cells may contribute to the pathogenesis of sepsis. Sepsis is a very serious systemic infectious disease by which severity is closely related to the host’s immune function. The postulated mechanisms by which different immune cells respond to sepsis might contribute to the development of sepsis are based on studies in vitro and animal models. The induction of autophagy in sepsis often promotes the immune response process of immune cells; while inhibition of autophagy or autophagy defects aggravates the inflammatory response and immunosuppression of sepsis. NETs, neutrophil extracellular traps.

Figure 2

Mitophagy and oxidative stress in damaged mitochondria. After the onset of sepsis, the number of damaged mitochondria increases. Damaged mitochondria cause mitochondrial dysfunction through ROS signaling pathways and mtDNA, causing a series of damage. Autophagy can remove damaged mitochondria. The process of autophagy is regulated by cytokines such as Nrf2 and SESN2. cGAS, cyclic GMP-AMP synthase; mtDNA, mitochondrial DNA; QC, quality control system.

Figure 3

The role of autophagy in different organs of sepsis. This figure is illustrated for humans, but the data is obtained from humans and other animals (mouse, rat, etc.). The protective or damaging effect of autophagy on organs in sepsis is our comprehensive judgment after literature analysis.