The emerging role of neutrophils in neurodegeneration

Neutrophils are the first line of defense in the innate immune system, helping to maintain tissue homeostasis as well as eliminating pathogens and self-components. The traditional view of neutrophils as simple phagocytes has been revised over the last decade as new research reveals their unappreciated complexity. Neutrophils are phenotypically and functionally heterogeneous, allowing them to act as modulators of both inflammation and immune responses. During acute inflammation, neutrophils perform a variety of beneficial effector functions, but when inflammation is induced by injury (sterile inflammation) the benefits of neutrophils in tissue repair are more controversial. In several pathological conditions, including cancer and autoimmune diseases, neutrophils can trigger harmful tissue damage. Interestingly, neutrophils are also key players in neuroinflammatory disorders, during which they transmigrate in the central nervous system, acquire a toxic phenotype, home in on neurons, and release harmful molecules that compromise neuronal functions. In this review, we discuss recent data that redefine the cell biology and phenotype of neutrophils, focusing on the role of these cells in multiple sclerosis and Alzheimer's disease, both of which feature strong neuroinflammatory components.