Eosinophil extracellular traps: heterogeneity of their stimuli, components, and functions

Eosinophils participate in immune regulation through their granule proteins and cytokines. Recent studies demonstrate eosinophil functional versatility through the mechanism of eosinophil extracellular traps (EETs). EET formation occurs via suicidal eosinophil extracellular trap cell death (EETosis) and vital EET release. EETs contain chromatin- or mitochondrial-derived DNA, granule proteins, nuclear proteins, and cytosolic components that vary depending on the type and intensity of stimuli. Synthetic compounds, pathogenic microorganisms, endogenous molecules, and co-stimulatory factors stimulate EET formation via diverse signaling pathways through receptors that rely on or operate independently of NADPH oxidase-mediated reactive oxygen species production and peptidylarginine deiminase-4-dependent histone modification. Necroptosis, pyroptosis, and autophagy pathways also contribute to EET biogenesis and subset heterogeneity. Here, we summarize EET formation, compositional profile, and functional heterogeneity across disease states, as well as the future potential for novel immune intervention.