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Macrophages recycle phagocytosed bacteria to fuel immunometabolic responses.

dc.rights.licenseopenen_US
hal.structure.identifierLaboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
dc.contributor.authorLESBATS, Juliette
hal.structure.identifierLaboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
dc.contributor.authorBRILLAC, Aurélia
dc.contributor.authorREISZ, Julie A
dc.contributor.authorMUKHERJEE, Parnika
hal.structure.identifierImmunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]
dc.contributor.authorLHUISSIER, Charlène
hal.structure.identifierBordeaux Imaging Center [BIC]
dc.contributor.authorFERNÁNDEZ-MONREAL, Mónica
hal.structure.identifierTBM-Core [Bordeaux] [UMS3427 - INSERM US005]
dc.contributor.authorDUPUY, Jean-William
hal.structure.identifierImmunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]
dc.contributor.authorSEQUEIRA, Angèle
hal.structure.identifierAlma Mater Studiorum Università di Bologna = University of Bologna [UNIBO]
hal.structure.identifierLaboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
dc.contributor.authorTIOLI, Gaia
dc.contributor.authorDE LA CALLE ARREGUI, Celia
hal.structure.identifierTBM-Core [Bordeaux] [UMS3427 - INSERM US005]
dc.contributor.authorPINSON, Benoît
dc.contributor.authorWENDISCH, Daniel
hal.structure.identifierUniversité de Bordeaux [UB]
hal.structure.identifierLaboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
dc.contributor.authorROUSSEAU, Benoit
dc.contributor.authorEFEYAN, Alejo
dc.contributor.authorSANDER, Leif Erik
dc.contributor.authorD'ALESSANDRO, Angelo
hal.structure.identifierImmunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]
hal.structure.identifierLaboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
dc.contributor.authorGARAUDE, Johan
dc.date.accessioned2025-05-30T08:06:06Z
dc.date.available2025-05-30T08:06:06Z
dc.date.issued2025-04-01
dc.identifier.issn1476-4687en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/206780
dc.description.abstractEnMacrophages 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.
dc.language.isoENen_US
dc.subject.enAnimals
dc.subject.enFemale
dc.subject.enMale
dc.subject.enMice
dc.subject.enAmino Acids
dc.subject.enAMP-Activated Protein Kinases
dc.subject.enBacteria
dc.subject.enCyclic AMP
dc.subject.enEnergy Metabolism
dc.subject.enGlutathione
dc.subject.enInterleukin-1beta
dc.subject.enMacrophages
dc.subject.enMechanistic Target of Rapamycin Complex 1
dc.subject.enMice
dc.subject.enInbred C57BL
dc.subject.enMicrobial Viability
dc.subject.enPhagocytosis
dc.subject.enPhagosomes
dc.subject.enRAW 264.7 Cells
dc.subject.enReactive Oxygen Species
dc.subject.enSuccinates
dc.title.enMacrophages recycle phagocytosed bacteria to fuel immunometabolic responses.
dc.title.alternativeNatureen_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1038/s41586-025-08629-4en_US
dc.subject.halSciences du Vivant [q-bio]/Génétiqueen_US
dc.identifier.pubmed40011782en_US
bordeaux.journalNatureen_US
bordeaux.page524-533en_US
bordeaux.volume640en_US
bordeaux.hal.laboratoriesMaladies Rares : Génétique et Métabolisme (MRGM) - UMR 1211en_US
bordeaux.issue8058en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.import.sourcepubmed
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exportfalse
workflow.import.sourcepubmed
dc.rights.ccCC BY-NC-NDen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Nature&rft.date=2025-04-01&rft.volume=640&rft.issue=8058&rft.spage=524-533&rft.epage=524-533&rft.eissn=1476-4687&rft.issn=1476-4687&rft.au=LESBATS,%20Juliette&BRILLAC,%20Aur%C3%A9lia&REISZ,%20Julie%20A&MUKHERJEE,%20Parnika&LHUISSIER,%20Charl%C3%A8ne&rft.genre=article


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