TY - JOUR
T1 - Neutrophils Fuel Effective Immune Responses through Gluconeogenesis and Glycogenesis
AU - Sadiku, Pranvera
AU - Willson, Joseph A.
AU - Ryan, Eilise M.
AU - Sammut, David
AU - Coelho, Patricia
AU - Watts, Emily R.
AU - Grecian, Robert
AU - Young, Jason M
AU - Bewley, Martin
AU - Arienti, Simone
AU - Mirchandani, Ananda S.
AU - Sanchez Garcia, Manuel A.
AU - Morrison, Tyler
AU - Zhang, Ailiang
AU - Reyes, Leila
AU - Griessler, Tobias
AU - Jheeta, Privjyot
AU - Paterson, Gordon G.
AU - Graham, Cristopher J.
AU - Thompson, John P.
AU - Baillie, Kenneth
AU - Thompson, A.A. Roger
AU - Morgan, Jessie-May
AU - Acosta-Sanchez, Abel
AU - Dardé, Veronica M.
AU - Duran, Jordi
AU - Guinovart, Joan J.
AU - Rodriguez-Blanco, Gio
AU - Von Kriegsheim, Alexander
AU - Meehan, Richard R.
AU - Mazzone, Massimiliano
AU - Dockrell, David H.
AU - Ghesquiere, Bart
AU - Carmeliet, Peter
AU - Whyte, Moira K.B.
AU - Walmsley, Sarah R.
PY - 2021/2/2
Y1 - 2021/2/2
N2 - 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.
AB - 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.
U2 - 10.1016/j.cmet.2020.11.016
DO - 10.1016/j.cmet.2020.11.016
M3 - Article
SN - 1550-4131
VL - 33
SP - 411-423.e4
JO - Cell Metabolism
JF - Cell Metabolism
IS - 2
ER -