title: Experimental Models of Foamy Macrophages and Approaches for Dissecting the Mechanisms of Lipid Accumulation and Consumption during Dormancy and Reactivation of Tuberculosis.
abstract: Despite a slight decline since 2014, tuberculosis (TB) remains the major deadly infectious disease worldwide with about 1.5 million deaths each year and with about one-third of the population being latently infected withMycobacterium tuberculosis, the etiologic agent of TB. During primo-infection, the recruitment of immune cells leads to the formation of highly organized granulomas. Among the different cells, one outstanding subpopulation is the foamy macrophage (FM), characterized by the abundance of triacylglycerol-rich lipid bodies (LB).M. tuberculosiscan reside in FM, where it acquires, from host LB, the neutral lipids which are subsequently processed and stored by the bacilli in the form of intracytosolic lipid inclusions (ILI). Although host LB can be viewed as a reservoir of nutrients for the pathogen during latency, the molecular mechanisms whereby intraphagosomal mycobacteria interact with LB and assimilate the LB-derived lipids are only beginning to be understood. Past studies have emphasized that these physiological processes are critical to theM. tuberculosisinfectious-life cycle, for propagation of the infection, establishment of the dormancy state and reactivation of the disease. In recent years, several animal and cellular models have been developed with the aim of dissecting these complex processes and of determining the nature and contribution of their key players. Herein, we review some of thein vitroandin vivomodels which allowed to gain significant insight into lipid accumulation and consumption inM. tuberculosis, two important events that are directly linked to pathogenicity, granuloma formation/maintenance and survival of the tubercle bacillus under non-replicative conditions. We also discuss the advantages and limitations of each model, hoping that this will serve as a guide for future investigations dedicated to persistence and innovative therapeutic approaches against TB.
authors: Aix-Marseille Université, Centre National de la Recherche Scientifique, EIPL Marseille, France.
authors: Pierre
authors: P
authors: Santucci
authors: Aix-Marseille Université, Centre National de la Recherche Scientifique, EIPLMarseille, France; Aix-Marseille Université, Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique, Institut de Recherche pour le Développement, URMITEMarseille, France.
authors: Feriel
authors: F
authors: Bouzid
authors: Aix-Marseille Université, Centre National de la Recherche Scientifique, EIPLMarseille, France; Centre d'études d'agents Pathogènes et Biotechnologies pour la Santé, Centre National de la Recherche Scientifique FRE3689, Université de MontpellierMontpellier, France.
authors: Nabil
authors: N
authors: Smichi
authors: Aix-Marseille Université, Centre National de la Recherche Scientifique, EIPL Marseille, France.
authors: Isabelle
authors: I
authors: Poncin
authors: Centre d'études d'agents Pathogènes et Biotechnologies pour la Santé, Centre National de la Recherche Scientifique FRE3689, Université de MontpellierMontpellier, France; Centre d'études d'agents Pathogènes et Biotechnologies pour la Santé, Institut National de la Santé et de la Recherche MédicaleMontpellier, France.
authors: Laurent
authors: L
authors: Kremer
authors: Aix-Marseille Université, Centre National de la Recherche Scientifique, EIPL Marseille, France.
authors: Chantal
authors: C
authors: De Chastellier
authors: Aix-Marseille Université, Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique, Institut de Recherche pour le Développement, URMITE Marseille, France.
authors: Michel
authors: M
authors: Drancourt
authors: Aix-Marseille Université, Centre National de la Recherche Scientifique, EIPL Marseille, France.
authors: Stéphane
authors: S
authors: Canaan
mesh_terms: D000818:Animals; D054884:Host-Pathogen Interactions; D006801:Humans; D050356:Lipid Metabolism; D008264:Macrophages / Q000378:metabolism* / Q000382:microbiology*; D008962:Models, Theoretical; D009169:Mycobacterium tuberculosis / Q000254:growth & development*
keywords: adipocyte; amoeba; granuloma; lipid body; mycobacteria; pathogenesis