Mechanisms regulating neutrophil survival and cell death

Neutrophils not only play a critical role as a first line of defense against bacteria and fungi infections but also contribute to tissue injury associated with autoimmune and inflammatory diseases. Neutrophils are rapidly and massively recruited from the circulation into injured tissues displaying an impressive arsenal of toxic weapons. Although effective in their ability to kill pathogens, these weapons were equally effective to induce tissue damage. Therefore, the inflammatory activity of neutrophils must be regulated with exquisite precision and timing, a task mainly achieved through a complex network of mechanisms, which regulate neutrophil survival. Neutrophils have the shortest lifespan among leukocytes and usually die via apoptosis although new forms of cell death have been characterized over the last few years. The lifespan of neutrophils can be dramatically modulated by a large variety of agents such as cytokines, pathogens, danger-associated molecular patterns as well as by pharmacological manipulation. Recent findings shed light about the complex mechanisms responsible for the regulation of neutrophil survival in different physiological, pathological, and pharmacological scenarios. Here, we provide an updated review on the current knowledge and new findings in this field and discuss novel strategies that could be used to drive the resolution of neutrophil-mediated inflammatory diseases.