Abstract

Immunological tests provide evidence of latent tuberculosis in one third of the global population, which corresponds to more than two billion individuals. Latent tuberculosis is defined by the absence of clinical symptoms but carries a risk of subsequent progression to clinical disease, particularly in the context of co-infection with HIV. In this Review we discuss the biology of latent tuberculosis as part of a broad range of responses that occur following infection with Mycobacterium tuberculosis, which result in the formation of physiologically distinct granulomatous lesions that provide microenvironments with differential ability to support or suppress the persistence of viable bacteria. We then show how this model can be used to develop a rational programme to discover effective drugs for the eradication of M. tuberculosis infection.

Author affiliations

1. Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
2. Novartis Institute for Tropical Diseases, 10 Biopolis Road, #05-01 Chromos, Singapore 138670.
3. Department of Microbiology and Immunology, Weill Cornell Medical College, New York, New York 10065, USA.
4. Department of Molecular Genetics and Biochemistry, Biomedical Science Tower, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.
5. Institute of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
6. Division of Mycobacterial Research, Medical Research Council National Institute for Medical Research, London NW7 1AA, UK.
7. Centre for Molecular Microbiology and Infection and Division of Medicine, Imperial College London SW7 2AZ, UK.

Correspondence to: Douglas Young^6,7 Email: d.young@imperial.ac.uk

Published online 26 October 2009

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