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Foamy macrophages and the progression of the human tuberculosis granuloma

Nature Immunology volume 10, pages 943–948 (2009)Cite this article

Abstract

The progression of tuberculosis from a latent, subclinical infection to active disease that culminates in the transmission of infectious bacilli is determined locally at the level of the granuloma. This progression takes place even in the face of a robust immune response that, although it contains infection, is unable to eliminate the bacterium. The factors or environmental conditions that influence this progression remain to be determined. Recent advances have indicated that pathogen-induced dysregulation of host lipid synthesis and sequestration serves a critical role in this transition. The foamy macrophage seems to be a key participant in both sustaining persistent bacteria and contributing to the tissue pathology that leads to cavitation and the release of infectious bacilli.

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Figure 1: Progression of the human tuberculosis granuloma.
Figure 2: In lesions from patients with tuberculosis, foamy macrophages are located mainly in the interface region surrounding central necrosis.
Figure 3: Vesicles containing Mtb-derived cell wall lipids are released from infected macrophages.
Figure 4: In foamy macrophages, tubercle bacilli–containing phagosomes have 'privileged' contact with cellular lipid bodies.
Figure 5: Model for caseum accumulation and granuloma progression.

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Acknowledgements

We thank C. de Chastellier and J.-F. Emile for the electron microscopy and histology in Figures 1 and 3. Supported by the European Union Framework Programme (Consortiums StopLATENT-TB Health-2007-200999 to P.-J.C.), the Bill and Melinda Gates Foundation Grand Challenges in Global Health (D.G.R., and GC12#82 to P.-J.C.), Institut National de la Santé et de la Recherche Médicale (Programme Interface to F.A.), Agence Nationale de la Recherche (ANR-06-MIME-A05115KS and ANR-06-MIME-037-01 to F.A.), the US Public Health Services (D.G.R.) and the US National Institutes of Health (HL055936 and AI064430 to D.G.R.).

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Authors and Affiliations

  1. Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA

    David G Russell & Mi-Jeong Kim

  2. Unitat de Tuberculosi Experimental, Institut Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Catalonia, Spain

    Pere-Joan Cardona

  3. Centro Investigaciones Biomédicas en Red Enfermedades Respiratorias, Palma de Mallorca, Spain

    Pere-Joan Cardona

  4. Institut National de la Santé et de la Recherche Médicale, Unité 892, Institut de Recherche Thérapeutique, Nantes, France

    Sophie Allain & Frédéric Altare

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Correspondence to David G Russell or Frédéric Altare.

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Russell, D., Cardona, PJ., Kim, MJ. et al. Foamy macrophages and the progression of the human tuberculosis granuloma. Nat Immunol 10, 943–948 (2009). https://doi.org/10.1038/ni.1781

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