title: Foamy macrophages from tuberculous patients' granulomas constitute a nutrient-rich reservoir for M. tuberculosis persistence.
abstract: Tuberculosis (TB) is characterized by a tight interplay between Mycobacterium tuberculosis and host cells within granulomas. These cellular aggregates restrict bacterial spreading, but do not kill all the bacilli, which can persist for years. In-depth investigation of M. tuberculosis interactions with granuloma-specific cell populations are needed to gain insight into mycobacterial persistence, and to better understand the physiopathology of the disease. We have analyzed the formation of foamy macrophages (FMs), a granuloma-specific cell population characterized by its high lipid content, and studied their interaction with the tubercle bacillus. Within our in vitro human granuloma model, M. tuberculosis long chain fatty acids, namely oxygenated mycolic acids (MA), triggered the differentiation of human monocyte-derived macrophages into FMs. In these cells, mycobacteria no longer replicated and switched to a dormant non-replicative state. Electron microscopy observation of M. tuberculosis-infected FMs showed that the mycobacteria-containing phagosomes migrate towards host cell lipid bodies (LB), a process which culminates with the engulfment of the bacillus into the lipid droplets and with the accumulation of lipids within the microbe. Altogether, our results suggest that oxygenated mycolic acids from M. tuberculosis play a crucial role in the differentiation of macrophages into FMs. These cells might constitute a reservoir used by the tubercle bacillus for long-term persistence within its human host, and could provide a relevant model for the screening of new antimicrobials against non-replicating persistent mycobacteria.
authors.affiliation: CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), Département Mécanismes Moléculaires des Infections Mycobactériennes, Toulouse, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Peyron
authors.forename: Julien
authors.initials: J
authors.lastname: Vaubourgeix
authors.forename: Yannick
authors.initials: Y
authors.lastname: Poquet
authors.forename: Florence
authors.initials: F
authors.lastname: Levillain
authors.forename: Catherine
authors.initials: C
authors.lastname: Botanch
authors.forename: Fabienne
authors.initials: F
authors.lastname: Bardou
authors.forename: Mamadou
authors.initials: M
authors.lastname: Daffé
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Emile
authors.forename: Bruno
authors.initials: B
authors.lastname: Marchou
authors.forename: Pere-Joan
authors.initials: PJ
authors.lastname: Cardona
authors.forename: Chantal
authors.initials: C
authors.lastname: de Chastellier
authors.forename: Frédéric
authors.initials: F
authors.lastname: Altare
mesh_terms: D002454:Cell Differentiation; D005487:Foam Cells / Q000382:microbiology*; D006099:Granuloma / Q000382:microbiology*; D006801:Humans; D008055:Lipids; D008264:Macrophages / Q000382:microbiology* / Q000473:pathology / Q000648:ultrastructure; D009164:Mycobacterium Infections / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000502:physiology; D009171:Mycolic Acids; D010587:Phagocytosis; D014376:Tuberculosis / Q000276:immunology / Q000382:microbiology*
chemical_list: D008055:Lipids; D009171:Mycolic Acids