An in vitro dual model of mycobacterial granulomas to investigate the molecular interactions between mycobacteria and human host cells

Authors

  • Marie-Pierre Puissegur,

    1. Department of Molecular Mechanisms of Mycobacterial Infections, Institut de Pharmacologie et de Biologie Structurale, CNRS UMR5089, 205, route de Narbonne, 31077 Toulouse, France.
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  • Catherine Botanch,

    1. Department of Molecular Mechanisms of Mycobacterial Infections, Institut de Pharmacologie et de Biologie Structurale, CNRS UMR5089, 205, route de Narbonne, 31077 Toulouse, France.
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  • Jean-Luc Duteyrat,

    1. Electron Microscopy Department, Rangueil Hospital Medical School, University of Toulouse, 31403 Toulouse, France.
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  • Georges Delsol,

    1. Department of Anatomy and Pathological Cytology, Purpan Hospital, 31300 Toulouse, France.
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  • Claude Caratero,

    1. Electron Microscopy Department, Rangueil Hospital Medical School, University of Toulouse, 31403 Toulouse, France.
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  • Frédéric Altare

    Corresponding author
    1. Department of Molecular Mechanisms of Mycobacterial Infections, Institut de Pharmacologie et de Biologie Structurale, CNRS UMR5089, 205, route de Narbonne, 31077 Toulouse, France.
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*E-mail frederic.altare@ipbs.fr; Tel. (+33) 5 61 17 54 63; Fax (+33) 5 61 17 59 94.

Summary

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.

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