Autophagy-driven NETosis is a double-edged sword - Review

Abstract

Autophagy is a cellular mechanism responsible for delivering protein aggregates or damaged organelles to lysosomes for degradation. It is also simultaneously a precise regulatory process, which is crucial for dealing with hunger, oxidative stress, and pathogen defense. Neutrophil Extracellular Traps (NETs), which form a part of a newly described bactericidal process, are reticular structures composed of a DNA backbone and multiple functional proteins, formed via a process known as NETosis. NETs exert their anti-infection activity by capturing pathogenic microorganisms, inhibiting their spread and inactivating virulence factors. However, NETs may also activate an immune response in non-infectious diseases, leading to tissue damage. Although the mechanism underlying this phenomenon is unclear, a large number of studies have suggested that autophagy may be involved. Autophagy-mediated NETs not only induce inflammation and tissue damage, but can also lead to cell senescence, malignant transformation, and cell death. Autophagy-dependent NETs also play a beneficial role in the hostwith respect to pathogen clearance and immune defense. Through careful review of the literature, we have found that the distinct roles of autophagy in NETosis may be dependent on the extent of autophagy and the specific manner in which it was induced. This article summarizes numerous recent studies, and reviews the role of autophagy-driven NETosis in various diseases, in the hope that this will lead to the development of more effective treatments.

Keywords: Autophagy; Cell death; Infection; NETosis; NETs; Neutrophil.