Approaching Neutrophil Pyroptosis

[Display omitted] •Pyroptosis is a form of necrotic cell death which occurs upon inflammasome activation and cleavage of gasdermins.•Neutrophils are the most abundant human leukocytes.•Neutrophil undergo a variety of necrotic forms of cell death including formation of neutrophil extracellular traps (NETs).•Increasing evidence shows that neutrophils resist canonical pyroptosis.•It is unclear to which extent neutrophils undergo pyroptosis and what their resistance mechanisms are. All cells must die at some point, and the dogma is that they do it either silently via apoptosis or via pro-inflammatory, lytic forms of death. Amongst these lytic cell death pathways, pyroptosis is one of the best characterized. Pyroptosis depends on inflammatory caspases which activate members of the gasdermin family of proteins, and it is associated with the release of the pro-inflammatory cytokines interleukin (IL)-1β and IL-18. Pyroptosis is an essential component of innate immunity, it initiates and amplifies inflammation and it removes the replication niche for intracellular pathogens. Most of the literature on pyroptosis focuses on monocytes and macrophages. However, the most abundant phagocytes in humans are neutrophils. This review addresses whether neutrophils undergo pyroptosis and the underlying mechanisms. Furthermore, I discuss how and why neutrophils might be able to resist pyroptosis.