@article{cfa6a577cc0242f0a7f9507dc8491ec4,
title = "Neutrophils fuel effective immune responses through gluconeogenesis and glycogenesis",
abstract = "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 = "COPD, GYS1, gluconeogenesis, glycogen, glycogenesis, glycogenolysis, glycolysis, inflammation, neutrophil",
author = "Pranvera Sadiku and Willson, {Joseph A.} and Ryan, {Eilise M.} and David Sammut and Patricia Coelho and Watts, {Emily R.} and Robert Grecian and Young, {Jason M.} and Martin Bewley and Simone Arienti and Mirchandani, {Ananda S.} and {Sanchez Garcia}, {Manuel A.} and Tyler Morrison and Ailing Zhang and Leila Reyes and Tobias Griessler and Privjyot Jheeta and Paterson, {Gordon G.} and Graham, {Christopher J.} and Thomson, {John P.} and Kenneth Baillie and Thompson, {A. A.Roger} and Morgan, {Jessie May} and Abel Acosta-Sanchez and Dard{\'e}, {Veronica M.} and Jordi Duran and Guinovart, {Joan J.} and Gio Rodriguez-Blanco and {Von Kriegsheim}, Alex and Meehan, {Richard R.} and Massimiliano Mazzone and Dockrell, {David H.} and Bart Ghesquiere and Peter Carmeliet and Whyte, {Moira K.B.} and Walmsley, {Sarah R.}",
note = "Funding Information: We thank Sandra Schoors for providing guidance and help with the radioactive assays, Wesley Vermaelen and Camila Takeno Cologna for help with LC-MS analysis, and the QMRI Flow Cytometry Facility for help with flow cytometry. This work was principally supported by Wellcome Trust Clinical Fellowship awards, UK ( 098516 and 209220 to S.R.W.). The work of P. Carmeliet is supported by long-term structural Methusalem funding from the Flemish Government. The Apex 5 expedition was supported by funding from the JABBS and Sylvia Waddilove Foundations, UK. Work in R.R.M.{\textquoteright}s lab is supported by Medical Research Council (MC_PC_U127574433 and MC_UU_0007/17), UK. Publisher Copyright: {\textcopyright} 2020 The Authors",
year = "2021",
month = feb,
day = "2",
doi = "10.1016/j.cmet.2020.11.016",
language = "English",
volume = "33",
pages = "411--423.e4",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "2",
}
