Autophagy in neutrophils: From granulopoiesis to neutrophil extracellular traps

Abstract

Autophagy is an evolutionarily conserved intracellular degradation system aiming to maintain cell homeostasis in response to cellular stress. At physiological states, basal or constitutive level of autophagy activity is usually low; however, it is markedly up-regulated in response to oxidative stress, nutrient starvation, and various immunological stimuli including pathogens. Many studies over the last years have indicated the implication of autophagy in a plethora of cell populations and functions. In this review, we focus on the role of autophagy in the biology of neutrophils. Early studies provided a link between autophagy and neutrophil cell death, a process essential for resolution of inflammation. Since then, several lines of evidence both in the human system and in murine models propose a critical role for autophagy in neutrophil-driven inflammation and defense against pathogens. Autophagy is essential for major neutrophil functions, including degranulation, reactive oxygen species production, and release of neutrophil extracellular traps. Going back to neutrophil generation in the bone marrow, autophagy plays a critical role in myelopoiesis, driving the differentiation of progenitor cells of the myeloid lineage toward neutrophils. Taken together, in this review we discuss the functional role of autophagy in neutrophils throughout their life, from their production in the bone marrow to inflammatory responses and NETotic cell death.