Macrophages recycle phagocytosed bacteria to fuel immunometabolic responses.
LESBATS, Juliette
Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
BRILLAC, Aurélia
Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
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Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
LESBATS, Juliette
Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
BRILLAC, Aurélia
Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
LHUISSIER, Charlène
Immunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]
Immunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]
SEQUEIRA, Angèle
Immunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]
Immunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]
TIOLI, Gaia
Alma Mater Studiorum Università di Bologna = University of Bologna [UNIBO]
Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
Alma Mater Studiorum Università di Bologna = University of Bologna [UNIBO]
Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
ROUSSEAU, Benoit
Université de Bordeaux [UB]
Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
Université de Bordeaux [UB]
Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
GARAUDE, Johan
Immunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]
Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
< Réduire
Immunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]
Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
Langue
EN
Article de revue
Ce document a été publié dans
Nature. 2025-04-01, vol. 640, n° 8058, p. 524-533
Résumé en anglais
Macrophages specialize in phagocytosis, a cellular process that eliminates extracellular matter, including microorganisms, through internalization and degradation. Despite the critical role of phagocytosis during bacterial ...Lire la suite >
Macrophages specialize in phagocytosis, a cellular process that eliminates extracellular matter, including microorganisms, through internalization and degradation. Despite the critical role of phagocytosis during bacterial infection, the fate of phagocytosed microbial cargo and its impact on the host cell are poorly understood. In this study, we show that ingested bacteria constitute an alternative nutrient source that skews immunometabolic host responses. By tracing stable isotope-labelled bacteria, we found that phagolysosomal degradation of bacteria provides carbon atoms and amino acids that are recycled into various metabolic pathways, including glutathione and itaconate biosynthesis, and satisfies the bioenergetic needs of macrophages. Metabolic recycling of microbially derived nutrients is regulated by the nutrient-sensing mechanistic target of rapamycin complex C1 and is intricately tied to microbial viability. Dead bacteria, as opposed to live bacteria, are enriched in cyclic adenosine monophosphate, sustain the cellular adenosine monophosphate pool and subsequently activate adenosine monophosphate protein kinase to inhibit the mechanistic target of rapamycin complex C1. Consequently, killed bacteria strongly fuel metabolic recycling and support macrophage survival but elicit decreased reactive oxygen species production and reduced interleukin-1β secretion compared to viable bacteria. These results provide a new insight into the fate of engulfed microorganisms and highlight a microbial viability-associated metabolite that triggers host metabolic and immune responses. Our findings hold promise for shaping immunometabolic intervention for various immune-related pathologies.< Réduire
Mots clés en anglais
Animals
Female
Male
Mice
Amino Acids
AMP-Activated Protein Kinases
Bacteria
Cyclic AMP
Energy Metabolism
Glutathione
Interleukin-1beta
Macrophages
Mechanistic Target of Rapamycin Complex 1
Mice
Inbred C57BL
Microbial Viability
Phagocytosis
Phagosomes
RAW 264.7 Cells
Reactive Oxygen Species
Succinates
Unités de recherche