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. Thompson; Kenneth 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

doi:10.1016/j.cmet.2020.11.016

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 journal › Article › peer-review

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.

Original language	English
Pages (from-to)	411-423.e4
Journal	Cell Metabolism
Volume	33
Issue number	2
Early online date	10 Dec 2020
DOIs	https://doi.org/10.1016/j.cmet.2020.11.016
Publication status	Published - 2 Feb 2021

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https://pubmed.ncbi.nlm.nih.gov/33306983/

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Defining the interplay between hypoxia and metabolic adaptations of the innate immune response.
Walmsley, S.
UK-based charities
1/01/18 → 31/12/22
Project: Research
Transfer from Sheffield: Regulation or neutrophilic inflammation by the HIF/PHD pathway
Walmsley, S.
UK-based charities
1/09/14 → 31/12/17
Project: Research

Alex Von Kriegsheim
- Deanery of Molecular, Genetic and Population Health Sciences - Group Leader / Mass Spectrometry Facility Manager
- Edinburgh Cancer Research Centre
Person: Academic: Research Active

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Sadiku, P., Willson, J. A., Ryan, E. M., Sammut, D., Coelho, P., Watts, E. R., Grecian, R., Young, J. M., Bewley, M., Arienti, S., Mirchandani, A. S., Sanchez Garcia, M. A., Morrison, T., Zhang, A., Reyes, L., Griessler, T., Jheeta, P., Paterson, G. G., Graham, C. J., ... Walmsley, S. R. (2021). Neutrophils Fuel Effective Immune Responses through Gluconeogenesis and Glycogenesis. Cell Metabolism, 33(2), 411-423.e4. https://doi.org/10.1016/j.cmet.2020.11.016

Sadiku, Pranvera ; Willson, Joseph A. ; Ryan, Eilise M. ; Sammut, David ; Coelho, Patricia ; Watts, Emily R. ; Grecian, Robert ; Young, Jason M ; Bewley, Martin ; Arienti, Simone ; Mirchandani, Ananda S. ; Sanchez Garcia, Manuel A. ; Morrison, Tyler ; Zhang, Ailiang ; Reyes, Leila ; Griessler, Tobias ; Jheeta, Privjyot ; Paterson, Gordon G. ; Graham, Cristopher J. ; Thompson, John P. ; Baillie, Kenneth ; Thompson, A.A. Roger ; Morgan, Jessie-May ; Acosta-Sanchez, Abel ; Dardé, Veronica M. ; Duran, Jordi ; Guinovart, Joan J. ; Rodriguez-Blanco, Gio ; Von Kriegsheim, Alexander ; Meehan, Richard R. ; Mazzone, Massimiliano ; Dockrell, David H. ; Ghesquiere, Bart ; Carmeliet, Peter ; Whyte, Moira K.B. ; Walmsley, Sarah R. / Neutrophils Fuel Effective Immune Responses through Gluconeogenesis and Glycogenesis. In: Cell Metabolism. 2021 ; Vol. 33, No. 2. pp. 411-423.e4.

@article{159bd9045532495b9158d43a9739db2c,

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.",

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 Ailiang Zhang and Leila Reyes and Tobias Griessler and Privjyot Jheeta and Paterson, {Gordon G.} and Graham, {Cristopher J.} and Thompson, {John P.} and Kenneth Baillie and Thompson, {A.A. Roger} and Jessie-May Morgan and Abel Acosta-Sanchez and Dard{\'e}, {Veronica M.} and Jordi Duran and Guinovart, {Joan J.} and Gio Rodriguez-Blanco and {Von Kriegsheim}, Alexander 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.}",

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doi = "10.1016/j.cmet.2020.11.016",

language = "English",

volume = "33",

pages = "411--423.e4",

journal = "Cell Metabolism",

issn = "1550-4131",

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Sadiku, P, Willson, JA, Ryan, EM, Sammut, D, Coelho, P, Watts, ER, Grecian, R, Young, JM, Bewley, M, Arienti, S, Mirchandani, AS , Sanchez Garcia, MA , Morrison, T , Zhang, A, Reyes, L, Griessler, T, Jheeta, P, Paterson, GG, Graham, CJ, Thompson, JP, Baillie, K, Thompson, AAR, Morgan, J-M, Acosta-Sanchez, A, Dardé, VM, Duran, J, Guinovart, JJ, Rodriguez-Blanco, G, Von Kriegsheim, A , Meehan, RR, Mazzone, M, Dockrell, DH, Ghesquiere, B, Carmeliet, P, Whyte, MKB & Walmsley, SR 2021, 'Neutrophils Fuel Effective Immune Responses through Gluconeogenesis and Glycogenesis', Cell Metabolism, vol. 33, no. 2, pp. 411-423.e4. https://doi.org/10.1016/j.cmet.2020.11.016

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

In: Cell Metabolism, Vol. 33, No. 2, 02.02.2021, p. 411-423.e4.

Research output: Contribution to journal › Article › peer-review

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

VL - 33

SP - 411-423.e4

JO - Cell Metabolism

JF - Cell Metabolism

SN - 1550-4131

IS - 2

ER -

Neutrophils Fuel Effective Immune Responses through Gluconeogenesis and Glycogenesis

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Defining the interplay between hypoxia and metabolic adaptations of the innate immune response.

Transfer from Sheffield: Regulation or neutrophilic inflammation by the HIF/PHD pathway

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Alex Von Kriegsheim

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