Live fast, die young: neutrophils streamline their metabolism to maximize inflammation.

Abstract

Neutrophils are the most abundant leukocytes at sites of inflammation and form the front line of the innate immune response. Neutrophils have a relatively short lifespan compared to other cell types, as they have streamlined their metabolic processes to support an arsenal of antimicrobial functions to combat invading pathogens at the cost of maximizing ATP output. To elicit antimicrobial stress, neutrophils rewire their glycolytic pathways to sustain phagocytosis and the oxidative burst and modify their mitochondrial metabolism to dictate degranulation or release of neutrophil extracellular traps. While many of these effector functions are sufficient to protect the "healthy" host from infection, chronic diseases disrupting metabolic and inflammatory homeostasis render the host susceptible to more frequent and severe bacterial infections. With the growing incidence of many metabolic and autoimmune diseases, a clearer understanding of the mechanisms regulating or disrupting neutrophil antimicrobial processes is required. This review focuses on the relationship between neutrophil function and metabolism and what is known about how this impacts autoimmune and metabolic diseases and/or disorders in the case of bacterial infection.