Neutrophils Fuel Effective Immune Responses through Gluconeogenesis and Glycogenesis

Pranvera Sadiku, Joseph A. Willson, Eilise M. Ryan, David Sammut, Patricia Coelho, Emily R. Watts, Robert Grecian, Jason M Young, Martin Bewley, Simone Arienti, Ananda S. Mirchandani, Manuel A. Sanchez Garcia, Tyler Morrison, Ailiang Zhang, Leila Reyes, Tobias Griessler, Privjyot Jheeta, Gordon G. Paterson, Cristopher J. Graham, John P. ThompsonKenneth Baillie, A.A. Roger Thompson, Jessie-May Morgan, Abel Acosta-Sanchez, Veronica M. Dardé, Jordi Duran, Joan J. Guinovart, Gio Rodriguez-Blanco, Alexander Von Kriegsheim, Richard R. Meehan, Massimiliano Mazzone, David H. Dockrell, Bart Ghesquiere, Peter Carmeliet, Moira K.B. Whyte, Sarah R. Walmsley

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.
Original languageEnglish
Pages (from-to)411-423.e4
JournalCell Metabolism
Volume33
Issue number2
Early online date10 Dec 2020
DOIs
Publication statusPublished - 2 Feb 2021

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