Neutrophils Fuel Effective Immune Responses through Gluconeogenesis and Glycogenesis

Neutrophils can function and survive in injured and infected tissues, where oxygen and metabolic substrates are limited. Using radioactive flux assays and LC-MS tracing with U-C-13 glucose, glutamine, and pyruvate, we observe that neutrophils require the generation of intracellular glycogen stores by gluconeogenesis and glycogenesis for effective survival and bacterial killing. These metabolic adaptations are dynamic, with net increases in glycogen stores observed following LPS challenge or altitude-induced hypoxia. Neutrophils from patients with chronic obstructive pulmonary disease have reduced glycogen cycling, resulting in impaired function. Metabolic specialization of neutrophils may therefore underpin disease pathology and

Automated summary

Recent research has shown that neutrophils can effectively survive and kill bacteria in injured and infected tissues by generating intracellular glycogen stores through gluconeogenesis and glycogenesis. Additionally, reduced glycogen cycling in neutrophils from patients with chronic obstructive pulmonary disease may be associated with impaired function.