01945nas a2200265   4500000000100000008004100001260001200042653002800054653002100082653001500103653001700118653001700135100001300152700001600165700001200181700001500193700001300208700001200221245009900233856008100332300001100413490000700424520123400431022001401665       2021                            d  c01/202110ahost-directed therapies10aimmunometabolism10amacrophage10amycobacteria10atuberculosis1 aLlibre A1 aDedicoat MJ1 aBurel J1 aDemangel C1 aO'Shea M1 aMauro C00aHost Immune-Metabolic Adaptations Upon Mycobacterial Infections and Associated Co-Morbidities.  uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8495197/pdf/fimmu-12-747387.pdf  a7473870 v123 a<p>Mycobacterial diseases are a major public health challenge. Their causative agents include, in order of impact, members of the  complex (causing tuberculosis),  (causing leprosy), and non-tuberculous mycobacterial pathogens including  Macrophages are mycobacterial targets and they play an essential role in the host immune response to mycobacteria. This review aims to provide a comprehensive understanding of the immune-metabolic adaptations of the macrophage to mycobacterial infections. This metabolic rewiring involves changes in glycolysis and oxidative metabolism, as well as in the use of fatty acids and that of metals such as iron, zinc and copper. The macrophage metabolic adaptations result in changes in intracellular metabolites, which can post-translationally modify proteins including histones, with potential for shaping the epigenetic landscape. This review will also cover how critical tuberculosis co-morbidities such as smoking, diabetes and HIV infection shape host metabolic responses and impact disease outcome. Finally, we will explore how the immune-metabolic knowledge gained in the last decades can be harnessed towards the design of novel diagnostic and therapeutic tools, as well as vaccines.</p>  a1664-3224