Luciana Balboa Poster 2023

Dr Luciana Balboa

Institute of Experimental Medicine (IMEX), CONICET-National Academy of Medicine, Argentina

Rewiring of Macrophage Metabolism By Lipid Mediators Derived From Omega-3 Fatty Acids: Its Impact on The Control Of Mycobacterium Tuberculosis Infection

Poster Abstract

The success of M. tuberculosis (Mtb) as a pathogen derives from its efficient adaptation to the intracellular milieu of macrophages, entailing the regulation of their metabolic pathways. Previously, we found that M1 macrophages exposed to the acellular fraction of pleural effusions from TB patients (TB-PE) displayed a reduced glycolytic activity and an increased mitochondrial respiration by targeting HIF-1α expression, and ultimately impairing the resistance to infection. Such properties were driven by polyunsaturated fatty acids (PUFA) metabolites, and herein, we aim to identify them. For this purpose, were determined PUFA metabolites within TB-PE by LC-MS/MS. The abundances of the omega-3-derived pro-resolving mediators 18-HEPE, 7(R)-Maresin 1, Protectin Dx and Resolvin D5 correlated with the inhibition of M1 macrophages’ glycolysis. To explore their implication in the regulation of the M1 metabolism, monocyte-derived macrophages were stimulated with LPS/IFN-γ for 24h (M1 profile) in the presence or not of those lipids, and the metabolic profile was assessed by the SCENITH method. Alternatively, macrophages were infected with Mtb. Unlike 7MaR1 and PDx, RvD5 and 18-HEPE reduced the glycolytic activity by M1 macrophages, leading to an increased mitochondrial respiration as well as high intracellular bacillary loads, features that could be reverted after the chemical stabilization of HIF-1α. Finally, we determined the ex vivo metabolism of CD14+ cells from paired TB pleural effusions and blood samples and found that pleural CD14+ cells showed a lower glycolytic capacity and a higher mitochondrial dependency than their blood counterpart. Unravelling the mechanisms by which lipids found in a TB microenvironment can drive metabolic alterations of macrophages leading to poor local protection will significantly advance knowledge on TB immunity.

Biography

After completing my degree as a biologist of the University of Buenos Aires, I started a PhD program in the group of Dr. Sasiain (Institute of Experimental Medicine, IMEX, CONICET-National Academy of Medicine, Buenos Aires), dedicated to the study of the mechanisms that regulate the immune response in TB. During my doctoral (2007-2012) and postdoctoral training (2012-2014), I studied the role of monocytes and their derived cells (macrophages and dendritic cells) in the regulation of the immune response against M. tuberculosis. I complemented my research based on the use of human samples with experimental mice models by developing part of my doctorate at the Hannover Faculty of Medicine in Germany (6 months) and part of my post-doctorate at the Dr. Hernández-Pando’ lab in Mexico (6 months). In 2014 we stablished a fruitful collaboration with the team led by Dr. Olivier Neyrolles (IPBS, Toulouse, France) to elucidate mechanisms driven by TB-associated microenvironments that are responsible for shifting the activation state of macrophages by studying the therapeutically aspirated pleural fluid from TB patients. Together we created an International Associated Laboratory in 2017. For the past 5 years, I focused my research on immunometabolic mechanisms in TB. I currently work as an Associate Researcher in Infectious Diseases at the IMEX in Buenos Aires, Argentina. I am a member of the Steering Committee of the Latin-American Society of Tuberculosis and other Mycobacteriosis, current co-Chair of the Young Academy of Argentina, and a member of the Global Young Academy, organizations aimed to give a voice to young scientists across the globe. Based on my contributions to the field of TB and my commitment to the public communication of science, I was awarded the Leonard Rieser Young Scientist Award 2021, given by the INTERCIENCIA Association, a Federation of Associations for Advancement of Science in the Americas.