000125329 001__ 125329
000125329 005__ 20240705134225.0
000125329 0247_ $$2doi$$a10.3389/fimmu.2022.1044592
000125329 0248_ $$2sideral$$a133059
000125329 037__ $$aART-2023-133059
000125329 041__ $$aeng
000125329 100__ $$aMendonca, Laura E.
000125329 245__ $$aHuman alveolar macrophage metabolism is compromised during Mycobacterium tuberculosis infection
000125329 260__ $$c2023
000125329 5060_ $$aAccess copy available to the general public$$fUnrestricted
000125329 5203_ $$aPulmonary macrophages have two distinct ontogenies: long-lived embryonically-seeded alveolar macrophages (AM) and bone marrow-derived macrophages (BMDM). Here, we show that after infection with a virulent strain of Mycobacterium tuberculosis (H37Rv), primary murine AM exhibit a unique transcriptomic signature characterized by metabolic reprogramming distinct from conventional BMDM. In contrast to BMDM, AM failed to shift from oxidative phosphorylation (OXPHOS) to glycolysis and consequently were unable to control infection with an avirulent strain (H37Ra). Importantly, healthy human AM infected with H37Ra equally demonstrated diminished energetics, recapitulating our observation in the murine model system. However, the results from seahorse showed that the shift towards glycolysis in both AM and BMDM was inhibited by H37Rv. We further demonstrated that pharmacological (e.g. metformin or the iron chelator desferrioxamine) reprogramming of AM towards glycolysis reduced necrosis and enhanced AM capacity to control H37Rv growth. Together, our results indicate that the unique bioenergetics of AM renders these cells a perfect target for Mtb survival and that metabolic reprogramming may be a viable host targeted therapy against TB.
000125329 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000125329 592__ $$a1.868$$b2023
000125329 593__ $$aImmunology and Allergy$$c2023$$dQ1
000125329 593__ $$aImmunology$$c2023$$dQ1
000125329 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000125329 700__ $$aPernet, Erwan
000125329 700__ $$aKhan, Nargis
000125329 700__ $$0(orcid)0000-0002-2980-9685$$aSanz, Joaquin$$uUniversidad de Zaragoza
000125329 700__ $$aKaufmann, Eva
000125329 700__ $$aDowney, Jeffrey
000125329 700__ $$aGrant, Alexandre
000125329 700__ $$aOrlova, Marianna
000125329 700__ $$aSchurr, Erwin
000125329 700__ $$aKrawczyk, Connie
000125329 700__ $$aJones, Russell G.
000125329 700__ $$aBarreiro, Luis B.
000125329 700__ $$aDivangahi, Maziar
000125329 7102_ $$12004$$2405$$aUniversidad de Zaragoza$$bDpto. Física Teórica$$cÁrea Física Teórica
000125329 773__ $$g13 (2023), 1044592 [13 pp.]$$pFront. immunol.$$tFrontiers in Immunology$$x1664-3224
000125329 8564_ $$s4524332$$uhttps://zaguan.unizar.es/record/125329/files/texto_completo.pdf$$yVersión publicada
000125329 8564_ $$s2044370$$uhttps://zaguan.unizar.es/record/125329/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000125329 909CO $$ooai:zaguan.unizar.es:125329$$particulos$$pdriver
000125329 951__ $$a2024-07-05-12:55:31
000125329 980__ $$aARTICLE