Glycogenesis and glyconeogenesis from glutamine, lactate and glycerol support human macrophage functions
Macrophages fight infection and ensure tissue repair, often operating at nutrient-poor wound sites. We investigated the ability of human macrophages to metabolize glycogen. We observed that the cytokines GM-CSF and M-CSF plus IL-4 induced glycogenesis and the accumulation of glycogen by monocyte-derived macrophages. Glyconeogenesis occurs in cells cultured in the presence of the inflammatory cytokines GM-CSF and IFNγ (M1 cells), via phosphoenolpyruvate carboxykinase 2 (PCK2) and fructose-1,6-bisphosphatase 1 (FBP1). Enzyme inhibition with drugs or gene silencing techniques and <sup>13</sup>C-tracing demonstrate that glutamine (metabolized by the TCA cycle), lactic acid, and glycerol were substrates of glyconeogenesis only in M1 cells. Tumor-associated macrophages (TAMs) also store glycogen and can perform glyconeogenesis. Finally, macrophage glycogenolysis and the pentose phosphate pathway (PPP) support cytokine secretion and phagocytosis regardless of the availability of extracellular glucose. Thus, glycogen metabolism supports the functions of human M1 and M2 cells, with inflammatory M1 cells displaying a possible dependence on glyconeogenesis.
Authors
- Pascale Jeannin (ORCID: https://orcid.org/0000-0002-3666-3856)
- Guillaume G. B. Tcherkez (ORCID: https://orcid.org/0000-0002-3339-956X)
- Naïg Guéguen (ORCID: https://orcid.org/0000-0002-3094-8121)
- Marie‐Christine Copin (ORCID: https://orcid.org/0000-0002-4729-7054)
- Charlotte Roy (ORCID: https://orcid.org/0000-0002-8528-9995)
- Simon Blanchard (ORCID: https://orcid.org/0000-0002-7953-0455)
- Guillaume Mabilleau (ORCID: https://orcid.org/0000-0003-1445-329X)
- Pascale Pignon
- Aurélie Moreau (ORCID: https://orcid.org/0000-0002-8519-2632)
- Yves Delneste (ORCID: https://orcid.org/0000-0002-2142-596X)
- Dominique Couez
- Laurence Preisser
- Laëtitia Basset (ORCID: https://orcid.org/0000-0001-7996-6470)
- Cinzia Bocca (ORCID: https://orcid.org/0000-0002-8822-9832)
- Guy Lenaers (ORCID: https://orcid.org/0000-0003-2736-3349)
- Cyril Abadie (ORCID: https://orcid.org/0000-0002-0416-6337)
- Najia Jeroundi
- Julie Lalande
Institutions
- Australian National University (AU)
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Université Nantes Angers Le Mans (FR)
- Institut Agro Rennes-Angers (FR)
- Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes Angers (FR)
- Institut de Transplantation Urologie en Nephrologie (FR)
- Centre Hospitalier Universitaire d'Angers (FR)
- Université d'Angers (FR)
- Nantes Université (FR)
Publication Details
- Journal
- EMBO Reports
- Published
- 2024-10-18
- DOI
- https://doi.org/10.1038/s44319-024-00278-4
- Citations
- 11
- Primary Topic
- Immune cells in cancer
- Type
- article
- Field-Weighted Citation Impact
- 2.65
Funders
- Agence Nationale de la Recherche
- Institut National de la Santé et de la Recherche Médicale
- Universite Angers
- Labex Immuno-Oncology