TY - JOUR T1 - Mycobacterium tuberculosis modulates mitochondrial function in human macrophages JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.congress-2020.2807 VL - 56 IS - suppl 64 SP - 2807 AU - Claudio Bussi AU - Mariana Silva Dos Santos AU - Elliott M. Bernard AU - Pierre Santucci AU - James I. Macrae AU - Maximiliano G. Gutierrez Y1 - 2020/09/07 UR - http://erj.ersjournals.com/content/56/suppl_64/2807.abstract N2 - Mitochondrial dynamics and metabolism in immune cells are closely associated. However, if these interactions play a role in the human macrophage response to Mycobacterium tuberculosis (Mtb) remains largely unknown.We used human induced-pluripotent stem cell derived macrophages (iPSDM) together with high-content live-cell imaging, extracellular flux analysis and unbiased metabolomics to investigate mitochondrial dynamics, Mtb intracellular replication and mitochondrial metabolism.Mitochondrial tracking at the single-cell level revealed extensive mitochondrial morphology heterogeneity. Surprisingly, Mtb did not induce significant changes in the mitochondrial area, length or width during the first 48h of infection. We did not find a correlation between Mtb intracellular replication and changes in mitochondrial morphological parameters. However, Mtb induced a decrease in the mitochondrial membrane potential and protein turnover rate, as visualised by MitoTracker Red and the ratiometric reporter MitoTimer, respectively.The metabolic profile of infected macrophages showed an increase in oxygen consumption and extracellular acidification rate after 48h of infection. These changes were associated with decreased mitochondrial protein and transcripts levels. The inhibition of glycolysis with 2-Deoxy-d-glucose promoted Mtb replication, whereas oxamate (lactate dehydrogenase inhibitor) impaired Mtb intracellular replication.Collectively, our results show that macrophage metabolic reprogramming is required for the control of Mtb replication. Unlike other intracellular pathogens, changes in host cell metabolism induced by Mtb might correlate with disruption of mitochondrial function rather than morphology.FootnotesCite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 2807.This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only). ER -