Current understanding in neutrophil differentiation and heterogeneity

Neutrophils are professional phagocytes that conduct effectors functions in the innate immune systems. They are differentiated in the bone marrow (BM) and terminally differentiated neutrophils are then released into systemic circulation. Neutrophils migrate into inflammatory foci through extravasation, reverse transmigration, and chemotaxis. As neutrophils arrive at a target site, they actively participate in eliminating pathogens. They phagocytose bacteria, and eliminate them through the generation of reactive oxygen species (ROS), release of protease-enriched granules, and formation of neutrophil extracellular traps (NETs). Since neutrophils are equipped with toxic arsenals, the activation of neutrophils is tightly controlled. Priming is the process of unlocking safety mechanisms before complete activation of neutrophils. Since the first discovery of neutrophils, they were considered as a homogeneous population with an inflammatory phenotype. However, heterogenous populations of neutrophils were discovered under physiological and pathological conditions. This review outlines the normal differentiation of neutrophils in the BM, and discusses the current understandings of neutrophil heterogeneity.