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, Ailing Zhang, Leila Reyes, Tobias Griessler, Privjyot Jheeta, Gordon G. Paterson, Christopher J. Graham, John P. ThomsonKenneth Baillie, A. A.Roger Thompson, Jessie May Morgan, Abel Acosta-Sanchez, Veronica M. Dardé, Jordi Duran, Joan J. Guinovart, Gio Rodriguez-Blanco, Alex Von Kriegsheim, Richard R. Meehan, Massimiliano Mazzone, David H. Dockrell, Bart Ghesquiere, Peter Carmeliet, Moira K.B. Whyte, Sarah R. Walmsley

Producción científica: Artículo en revista indizadaArtículorevisión exhaustiva

79 Citas (Web of Science)

Resumen

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.

Idioma originalInglés
Páginas (desde-hasta)411-423.e4
PublicaciónCell Metabolism
Volumen33
N.º2
Fecha en línea anticipada10 dic 2020
DOI
EstadoPublicada - 2 feb 2021
Publicado de forma externa

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