Main neutrophil subsets identified in the peripheral blood of patients with diseases. Mature neutrophils from healthy donors, after blood centrifugation over density gradients, typically sediment on top of red cells (arbitrarily indicated as NDNs in A). By contrast, immature neutrophils, as well as mature neutrophils activated in vivo under inflammatory settings, display altered cell buoyancy properties and thus sediment within the mononuclear cell fraction (arbitrarily indicated as LDNs in A). According to the literature, LDNs may include (1) immature neutrophils found in patients with sepsis and with function mostly undefined; (2) immunosuppressive neutrophil subsets, also known as G-MDSCs, found in cancer and HIV patients or in G-CSF–treated donors and displaying either immature or activated phenotypes; and (3) proinflammatory neutrophil subsets found in patients with autoimmune diseases, recently named LDGs and consisting of a mixed population of immature and mature cells. Circulating mature neutrophil subsets, displaying immunosuppressive properties, have also been identified within either the NDN fraction in cancer and HIV patients (A) or the total leukocytes (obtained after red cell lysis of whole blood) from healthy volunteers administered with endotoxin or from patients with severe injury, cancer, or HIV infection (arbitrarily indicated as UNs in B).