title: An in vitro dual model of mycobacterial granulomas to investigate the molecular interactions between mycobacteria and human host cells.
abstract: In the majority of individuals infected with Mycobacterium tuberculosis, the bacilli cause a long-term asymptomatic infection called latent tuberculosis, a state during which the bacilli reside within granulomas. Latently infected individuals have around 10% risk of progression to clinical disease at a later stage. Determining the state of the mycobacteria and the host cells during this latent phase, i.e. within the granulomas, would greatly improve our understanding of the physiopathology of tuberculosis, and thus enable the development of new therapeutic means to treat the one-third of the world's population who are latently infected. We have developed an in vitro model of human mycobacterial granulomas, enabling the cellular and molecular analysis of the very first steps in the host granulomatous response to either mycobacterial compounds or live mycobacterial species. In vitro mycobacterial granulomas mimic natural granulomas very well, with the progressive recruitment of macrophages around live bacilli or mycobacterial antigen-coated beads, their differentiation into multinucleated giant cells and epithelioid cells, and the final recruitment of a ring of activated lymphocytes. Besides morphological similarities, in vitro granulomas also functionally resemble natural ones, with the development of intense cellular co-operation and intracellular mycobactericidal activities.
authors.affiliation: Department of Molecular Mechanisms of Mycobacterial Infections, Institut de Pharmacologie et de Biologie Structurale, CNRS UMR5089, 205, route de Narbonne, 31077 Toulouse, France.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Puissegur
authors.forename: Catherine
authors.initials: C
authors.lastname: Botanch
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Duteyrat
authors.forename: Georges
authors.initials: G
authors.lastname: Delsol
authors.forename: Claude
authors.initials: C
authors.lastname: Caratero
authors.forename: Frédéric
authors.initials: F
authors.lastname: Altare
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology / Q000378:metabolism; D001500:BCG Vaccine / Q000378:metabolism; D002478:Cells, Cultured; D018450:Disease Progression; D006099:Granuloma / Q000382:microbiology* / Q000473:pathology; D006801:Humans; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000648:ultrastructure; D008213:Lymphocyte Activation; D009169:Mycobacterium tuberculosis / Q000502:physiology*; D012685:Sepharose / Q000378:metabolism; D014376:Tuberculosis / Q000276:immunology / Q000382:microbiology* / Q000473:pathology* / Q000628:therapy
chemical_list: D000942:Antigens, Bacterial; D001500:BCG Vaccine; D012685:Sepharose