Relationship between chemokine receptor expression, chemokine levels and HIV-1 replication in the lungs of persons exposed to Mycobacterium tuberculosis

Authors

  • Barbara Kalsdorf,

    Corresponding author
    1. Clinical Infectious Diseases Research Initiative, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Observatory, Cape Town, South Africa
    2. Clinical Infectious Diseases, Tuberculosis Center, Research Center Borstel, Borstel, Germany
    • Full correspondence: Dr. Barbara Kalsdorf, Clinical Infectious Diseases, Tuberculosis Center, Research Center Borstel, 23845 Borstel, Germany

      Fax: +49-4537 1883130

      e-mail: bkalsdorf@fz-borstel.de

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  • Keira H. Skolimowska,

    1. Clinical Infectious Diseases Research Initiative, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Observatory, Cape Town, South Africa
    2. Department of Medicine, Imperial College London, London, UK
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  • Thomas J. Scriba,

    1. South African Tuberculosis Vaccine Initiative and School of Child and Adolescent Health, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Observatory, Cape Town, South Africa
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  • Rod Dawson,

    1. Department of Medicine, University of Cape Town, Observatory, Cape Town, South Africa
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  • Keertan Dheda,

    1. Department of Medicine, University of Cape Town, Observatory, Cape Town, South Africa
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  • Kathryn Wood,

    1. Clinical Infectious Diseases Research Initiative, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Observatory, Cape Town, South Africa
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  • Jessica Hofmeister,

    1. Clinical Infectious Diseases, Tuberculosis Center, Research Center Borstel, Borstel, Germany
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  • Willem A. Hanekom,

    1. Clinical Infectious Diseases Research Initiative, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Observatory, Cape Town, South Africa
    2. South African Tuberculosis Vaccine Initiative and School of Child and Adolescent Health, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Observatory, Cape Town, South Africa
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  • Christoph Lange,

    1. University of Schleswig Holstein, Campus Lübeck, Lübeck, Germany
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  • Robert J. Wilkinson

    1. Clinical Infectious Diseases Research Initiative, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Observatory, Cape Town, South Africa
    2. Department of Medicine, Imperial College London, London, UK
    3. Department of Medicine, University of Cape Town, Observatory, Cape Town, South Africa
    4. MRC National Institute for Medical Research, London, UK
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  • The copyright line of the above article has been changed since first published on 13 December 2012. The correct copyright of this article is:

Abstract

Increased susceptibility to tuberculosis following HIV-1 seroconversion contributes significantly to the tuberculosis epidemic in sub-Saharan Africa. Lung-specific mechanisms underlying the interaction between HIV-1 and Mycobacterium tuberculosis infection are incompletely understood. Here we address these questions by examining the effect of HIV-1 and latent M. tuberculosis co-infection on the expression of viral-entry receptors and ligands in bronchoalveolar lavage (BAL) of HIV-1-infected and -uninfected patients with and without latent M. tuberculosis infection.

Irrespective of HIV-1 status, T cells from BAL expressed higher levels of the beta-chemokine receptor (CCR)5 than peripheral blood T cells, in particular the CD8+ T cells of HIV-1-infected persons showed elevated CCR5 expression. The concentrations of the CCR5 ligands RANTES and MIP-1β were elevated in the BAL of HIV-1-infected persons compared with that in HIV-1-uninfected controls. CCR5 expression and RANTES concentration correlated strongly with HIV-1 viral load in the BAL. In contrast, these alterations were not associated with M. tuberculosis sensitisation in vivo, nor did M. tuberculosis infection of BAL cells ex vivo change RANTES expression.

These data suggest ongoing HIV-1 replication predominantly drives local pulmonary CCR5+ T-cell activation in HIV/latent M. tuberculosis co-infection.

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