THE MICROENVIRONMENT OF M. TUBERCULOSIS INFECTION MODULATES THE METABOLIC PATHWAYS OF M1 MACROPHAGES

MARÍN FRANCO, JOSÉ LUIS; FERREYRA, MALENA; OSTROWSKI, MATÍAS; HERNANDEZ-PANDO, ROGELIO; SCHIERLOH, PABLO; LUGO-VILLARINO, GEANNCARLO; DUETTE, GABRIEL; PALMERO, DOMINGO; PATIÑO MARTINEZ, EDUARDO; PEDRAZA CHAVERRI, JOSÉ; SASIAIN, MARIA DEL CARMEN; GENOULA, MELANIE; MORAÑA, EDUARDO JOSE; APARICIO TREJO, OMAR EMILIANO; SANCHEZ-TORRES, CARMEN; NEYROLLES, OLIVIER; BALBOA, LUCIANA

Mar del Plata

Congreso; Reunión Conjunta SAIC SAI SAFIS 2018; 2018

Since metabolic pathways regulate macrophage biology, they may represent a target for pathogens to circumvent this leukocyte´s effector functions. Macrophage activation towards the pro-inflammatory and microbicidal (M1) program is accompanied by a metabolic shift towards glycolysis and away from oxidative phosphorylation (OXPHOS), a switch that is governed by HIF-1a. Herein we hypothesize that the microenvironment generated during infection with Mycobacterium tuberculosis, the etiological agent for tuberculosis (TB), leads to changes in the metabolic pathways of M1 macrophages and impairment of microbicidal activity. Our approach was to activate M1 human macrophages using IFN-γ/LPS in the presence of the acellular fraction of tuberculous pleural effusions (PE), a bona fide TB-associated microenvironment. We found that the release of lactate, the final glycolysis product, augmented in M1 macrophages, is reduced in the presence of tuberculous PE (p