| Autor: |
Marín Franco, José Luis, Genoula, Melanie, Corral, Dan, Duette, Gabriel, Ferreyra, Malena, Maio, Mariano, Dolotowicz, María Belén, Aparicio-Trejo, Omar Emiliano, Patiño-Martínez, Eduardo, Charton, Alison, Métais, Arnaud, Fuentes, Federico, Soldan, Vanessa, Moraña, Eduardo José, Palmero, Domingo, Ostrowski, Matías, Schierloh, Pablo, Sánchez-Torres, Carmen, Hernández-Pando, Rogelio, Pedraza-Chaverri, José |
| Zdroj: |
Cell Reports; Dec2020, Vol. 33 Issue 13, pN.PAG-N.PAG, 1p |
| Abstrakt: |
Mycobacterium tuberculosis (Mtb) regulates the macrophage metabolic state to thrive in the host, yet the responsible mechanisms remain elusive. Macrophage activation toward the microbicidal (M1) program depends on the HIF-1α-mediated metabolic shift from oxidative phosphorylation (OXPHOS) toward glycolysis. Here, we ask whether a tuberculosis (TB) microenvironment changes the M1 macrophage metabolic state. We expose M1 macrophages to the acellular fraction of tuberculous pleural effusions (TB-PEs) and find lower glycolytic activity, accompanied by elevated levels of OXPHOS and bacillary load, compared to controls. The eicosanoid fraction of TB-PE drives these metabolic alterations. HIF-1α stabilization reverts the effect of TB-PE by restoring M1 metabolism. Furthermore, Mtb-infected mice with stabilized HIF-1α display lower bacillary loads and a pronounced M1-like metabolic profile in alveolar macrophages (AMs). Collectively, we demonstrate that lipids from a TB-associated microenvironment alter the M1 macrophage metabolic reprogramming by hampering HIF-1α functions, thereby impairing control of Mtb infection. • Tuberculous pleural effusion (TB-PE) shifts glycolysis to OXPHOS in M1 macrophages • Metabolic shift is accompanied by low HIF-1α activity and high M. tuberculosis burden • HIF-1α stabilization reverts the metabolic shift and inhibitory effects of TB-PE • Host-derived lipids (eicosanoid-enriched fraction) in TB-PE drive the metabolic shift The metabolic state is a clear yet confounding factor in macrophages to control M. tuberculosis. In this issue, Marín Franco et al. reveal that a tuberculosis-associated microenvironment triggers the shift from aerobic glycolysis to OXPHOS by inhibiting HIF-1α activity, rendering M1 macrophages susceptible to M. tuberculosis infection. Host-derived lipids in this microenvironment are responsible for the metabolic shift and inhibitory effects on pro-inflammatory and microbicidal macrophage properties. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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