Cell Metabolism
Volume 33, Issue 2, 2 February 2021, Pages 411-423.e4
Journal home page for Cell Metabolism

Article
Neutrophils Fuel Effective Immune Responses through Gluconeogenesis and Glycogenesis

https://doi.org/10.1016/j.cmet.2020.11.016Get rights and content
Under a Creative Commons license
open access

Highlights

  • Neutrophils utilize gluconeogenesis (GNG) to generate glycogen stores

  • Glycogenesis is essential for neutrophil survival and function

  • Defective glycogen cycling impairs neutrophil function in COPD

  • Glycogen cycling underpins the metabolic specialization of neutrophils

Summary

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-13C 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 allow selective therapeutic targeting.

Keywords

neutrophil
glycogenesis
gluconeogenesis
inflammation
COPD
glycogen
glycolysis
glycogenolysis
GYS1

Cited by (0)

14

Lead Contact