Neutrophils Fuel Effective Immune Responses through Gluconeogenesis and Glycogenesis

  1. Ghesquiere, Bart
  2. Sanchez Garcia, Manuel A.
  3. Griessler, Tobias
  4. Mazzone, Massimiliano
  5. Walmsley, Sarah R.
  6. Duran, Jordi
  7. Morgan, Jessie-May
  8. Baillie, Kenneth
  9. Willson, Joseph A.
  10. Ryan, Eilise M.
  11. Dardé, Veronica M.
  12. Guinovart, Joan J.
  13. Watts, Emily R.
  14. Sammut, David
  15. Rodriguez-Blanco, Gio
  16. Meehan, Richard R.
  17. Coelho, Patricia
  18. Acosta-Sanchez, Abel
  19. Zhang, Ailing
  20. Dockrell, David H.
  21. Young, Jason M.
  22. Grecian, Robert
  23. Graham, Christopher J.
  24. Reyes, Leila
  25. Thompson, A.A. Roger
  26. Whyte, Moira K.B.
  27. Paterson, Gordon G.
  28. Arienti, Simone
  29. Mirchandani, Ananda S.
  30. Sadiku, Pranvera
  31. Morrison, Tyler
  32. Von Kriegsheim, Alex
  33. Carmeliet, Peter
  34. Jheeta, Privjyot
  35. Bewley, Martin
  36. Thomson, John P.
  37. Mostrar todos los/as autores/as +
Revista:
Cell Metabolism

ISSN: 1550-4131

Año de publicación: 2021

Volumen: 33

Número: 2

Páginas: 411-423.e4

Tipo: Artículo

DOI: 10.1016/J.CMET.2020.11.016 GOOGLE SCHOLAR lock_openAcceso abierto editor

Otras publicaciones en: Cell Metabolism

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.