Difference between revisions of "Franco 2020 bioRxiv"
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|title=Franco JLM, Genoula M, Corral D, Duette G, Ferreyra M, Maio M, Dolotowicz MB, Aparicio-Trejo OE, Patiño-Martínez E, Fuentes F, Soldan V, Moraña EJ, Palmero D, Ostrowski M, Schierloh P, Sánchez-Torres C, Hernández-Pando R, Pedraza-Chaverri J, Rombouts Y, Layre E, Hudrisier D, Vérollet C, Neyrolles O, Sasiain MC, Lugo-Villarino G, Balboa L (2020) Host-derived lipids from tuberculous pleurisy impair macrophage microbicidal-associated metabolic activity. bioRxiv doi: https://doi.org/10.1101/2020.03.23.001818 . | |title=Franco JLM, Genoula M, Corral D, Duette G, Ferreyra M, Maio M, Dolotowicz MB, Aparicio-Trejo OE, Patiño-Martínez E, Fuentes F, Soldan V, Moraña EJ, Palmero D, Ostrowski M, Schierloh P, Sánchez-Torres C, Hernández-Pando R, Pedraza-Chaverri J, Rombouts Y, Layre E, Hudrisier D, Vérollet C, Neyrolles O, Sasiain MC, Lugo-Villarino G, Balboa L (2020) Host-derived lipids from tuberculous pleurisy impair macrophage microbicidal-associated metabolic activity. bioRxiv doi: https://doi.org/10.1101/2020.03.23.001818 . | ||
|info=[https://www.biorxiv.org/content/10.1101/2020.03.23.001818v1 bioRxiv Open Access] | |info=[https://www.biorxiv.org/content/10.1101/2020.03.23.001818v1 bioRxiv Open Access] | ||
|authors=Franco JLM, Genoula M, Corral D, Duette G, Ferreyra M, Maio M, Dolotowicz MB, Aparicio-Trejo OE, | |authors=Franco JLM, Genoula M, Corral D, Duette G, Ferreyra M, Maio M, Dolotowicz MB, Aparicio-Trejo OE, Patino-Martinez E, Fuentes F, Soldan V, Morana EJ, Palmero D, Ostrowski M, Schierloh P, Sanchez-Torres C, Hernandez-Pando R, Pedraza-Chaverri J, Rombouts Y, Layre E, Hudrisier D, Verollet C, Neyrolles O, Sasiain MC, Lugo-Villarino G, Balboa L | ||
|year=2020 | |year=2020 | ||
|journal=bioRxiv | |journal=bioRxiv |
Revision as of 13:24, 6 May 2020
Franco JLM, Genoula M, Corral D, Duette G, Ferreyra M, Maio M, Dolotowicz MB, Aparicio-Trejo OE, Patiño-Martínez E, Fuentes F, Soldan V, Moraña EJ, Palmero D, Ostrowski M, Schierloh P, Sánchez-Torres C, Hernández-Pando R, Pedraza-Chaverri J, Rombouts Y, Layre E, Hudrisier D, Vérollet C, Neyrolles O, Sasiain MC, Lugo-Villarino G, Balboa L (2020) Host-derived lipids from tuberculous pleurisy impair macrophage microbicidal-associated metabolic activity. bioRxiv doi: https://doi.org/10.1101/2020.03.23.001818 . |
Franco JLM, Genoula M, Corral D, Duette G, Ferreyra M, Maio M, Dolotowicz MB, Aparicio-Trejo OE, Patino-Martinez E, Fuentes F, Soldan V, Morana EJ, Palmero D, Ostrowski M, Schierloh P, Sanchez-Torres C, Hernandez-Pando R, Pedraza-Chaverri J, Rombouts Y, Layre E, Hudrisier D, Verollet C, Neyrolles O, Sasiain MC, Lugo-Villarino G, Balboa L (2020) bioRxiv
Abstract: Mycobacterium tuberculosis (Mtb) regulates the macrophage metabolic state to thrive in the host. Yet, the responsible mechanisms remain elusive. Macrophage activation towards the microbicidal (M1) program depends on the HIF-1 α-mediated metabolic shift from oxidative phosphorylation towards glycolysis. Here, we asked whether a tuberculosis (TB) microenvironment changes the M1 macrophage metabolic state. We exposed M1 macrophages to the acellular fraction of tuberculous pleural effusions (TB-PE), and found lower glycolytic activity, accompanied by elevated levels of oxidative phosphorylation and bacillary load, compared to controls. The host-derived lipid fraction of TB-PE drove these metabolic alterations. HIF-1α stabilization reverted the effect of TB-PE by restoring M1 metabolism. As a proof-of-concept, Mtb-infected mice with stabilized HIF-1α displayed lower bacillary loads and a pronounced M1-like metabolic profile in alveolar macrophages. Collectively, we demonstrate that host-derived lipids from a TB-associated microenvironment alter the M1 macrophage metabolic reprogramming by hampering HIF-1α functions, thereby impairing control of Mtb infection. • Keywords: Macrophages, Tuberculosis, Oxygen consumption, Aerobic glycolytic, HIF-1α, Pleural effusion • Bioblast editor: Plangger M
Labels: MiParea: Respiration
HRR: Oxygraph-2k
2020-05