Editorial: The emerging role of metabolism and metabolic-related receptors on neutrophil extracellular traps (NET) formation

Abstract

Editorial on the Research TopicThe emerging role of metabolism and metabolic-related receptors on neutrophil extracellular traps formation Neutrophils play a central role in host innate immunity as first cell line to fight pathogens; however, they are also being responsible for "collateral damage". Neutrophils have a wide repertoire of biological responses, including reactive oxygen species (ROS)dependent and -independent effector mechanisms. Release of neutrophil extracellular traps (NET) has been added as key innate immune reaction. Understanding NET formation has broadened our knowledge regarding innate defence mechanisms as well as pathological mechanisms associated with occurrence of uncontrolled NET.Biological processes associated with neutrophil responses are closely linked to cellular metabolism. Glycolysis seems to be the main route associated with ATP generation, phagocytosis, and NET (1, 2), and the low abundance of mitochondria in neutrophils has led to the assumption that neutrophils exclusively rely on glycolysis for their biological functions (3). However, different metabolic routes are required to fulfil energetic, biosynthetic, and functional requirements of activated neutrophils, including TCA cycle, oxidative phosphorylation (OxPhos), pentose phosphate pathway (PPP), and fatty acid oxidation (FAO) (4). These metabolic pathways can generate metabolites that exert second messenger functions or act as ligands of receptors (e.g. purinergic receptors, succinate receptor SUCNR1 and lactate receptor HCA2) (5, 6).

Fasciola hepatica soluble antigens (FhAg) induce ovine PMN innate immune reactions and NET formation in vitro and in vivo

“…Nonetheless, different metabolic routes, including glycolysis with ATP generation, are required to fulfil energetic, biosynthesis, and defence functions of mammalian PMN [ 60 – 62 ]. Recently, it has been demonstrated that mammalian PMN can additionally rely on TCA cycle, oxidative phosphorylation (OXPHOS), pentose phosphate pathway (PPP), and fatty acid oxidation (FAO) for energy [ 63 , 64 ]. Overall, here we present new insights into early host innate immune response in vivo and in vitro of ovine PMN driven by F. hepatica considering ovine hosts as relevant and highly susceptible animals to fasciolosis.…”