Host-Derived Lipids from Tuberculous Pleurisy Impair Macrophage Microbicidal-Associated Metabolic Activity.
Animals
Bacterial Load
Eicosanoids
/ pharmacology
Female
Glycolysis
/ drug effects
Host-Pathogen Interactions
Humans
Hypoxia-Inducible Factor 1, alpha Subunit
/ metabolism
Lipids
/ pharmacology
Macrophage Activation
Macrophages
/ drug effects
Mice
Mice, Inbred C57BL
Mitochondria
/ drug effects
Mycobacterium tuberculosis
/ metabolism
Oxidative Phosphorylation
/ drug effects
Oxygen Consumption
/ drug effects
Pleural Effusion
Tuberculosis, Pleural
/ metabolism
HIF-1α
aerobic glycolytic
eicosanoids
macrophages
oxygen consumption
pleural effusion
tuberculosis
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
29 12 2020
29 12 2020
Historique:
received:
28
02
2020
revised:
18
10
2020
accepted:
02
12
2020
entrez:
30
12
2020
pubmed:
31
12
2020
medline:
14
10
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33378679
pii: S2211-1247(20)31536-9
doi: 10.1016/j.celrep.2020.108547
pii:
doi:
Substances chimiques
Eicosanoids
0
HIF1A protein, human
0
Hif1a protein, mouse
0
Hypoxia-Inducible Factor 1, alpha Subunit
0
Lipids
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
108547Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.