Neutrophils Fuel Effective Immune Responses through Gluconeogenesis and Glycogenesis
- Ghesquiere, Bart
- Sanchez Garcia, Manuel A.
- Griessler, Tobias
- Mazzone, Massimiliano
- Walmsley, Sarah R.
- Duran, Jordi
- Morgan, Jessie-May
- Baillie, Kenneth
- Willson, Joseph A.
- Ryan, Eilise M.
- Dardé, Veronica M.
- Guinovart, Joan J.
- Watts, Emily R.
- Sammut, David
- Rodriguez-Blanco, Gio
- Meehan, Richard R.
- Coelho, Patricia
- Acosta-Sanchez, Abel
- Zhang, Ailing
- Dockrell, David H.
- Young, Jason M.
- Grecian, Robert
- Graham, Christopher J.
- Reyes, Leila
- Thompson, A.A. Roger
- Whyte, Moira K.B.
- Paterson, Gordon G.
- Arienti, Simone
- Mirchandani, Ananda S.
- Sadiku, Pranvera
- Morrison, Tyler
- Von Kriegsheim, Alex
- Carmeliet, Peter
- Jheeta, Privjyot
- Bewley, Martin
- Thomson, John P.
- Mostrar todos os autores +
ISSN: 1550-4131
Ano de publicación: 2021
Volume: 33
Número: 2
Páxinas: 411-423.e4
Tipo: Artigo
Outras publicacións en: Cell Metabolism
Resumo
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.