Net amyloidogenic backbone in human activated neutrophils

Activated human neutrophils produce a fibrillar DNA network (NETs) for entrapping and killing bacteria, fungi, protozoa and viruses. Our results suggest that the neutrophil extracellular traps show a resistant amyloidogenic backbone utilized for addressing reputed proteins and DNA against the non-self. The formation of amyloid fibrils in neutrophils is regulated by the imbalance of reactive oxygen species in the cytoplasm. The intensity and the source of ROS signal is determinant for promoting stress-associated responses such as amyloidogenesis and closely related events: autophagy, exosome release, activation of ACTH/α-MSH loop and synthesis of specific cytokines. These interconnected responses in human activated neutrophils, that have been evaluated by a morpho-functional and quantitative point of view, represent primitive, but potent, innate defence mechanisms. In invertebrates, circulating phagocytic immune cells, when activated, show responses similar to that previously described for activated human neutrophils. Invertebrate cells, within endoplasmic reticulum cisternae, produce a fibrillar material then assembled into an amyloidogenic scaffold utilized to convey melanin close to the invader. These findings, in consideration to the critical role played by NET in the development of several pathologies, could explain the structural resistance of these scaffolds and could provide the basis for developing new diagnostic and therapeutic approaches in immunomediated diseases in which the innate branch of the immune system has a pivotal role. This article is protected by copyright. All rights reserved.