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

Eur J Immunol. 2013 Feb;43(2):540-9. doi: 10.1002/eji.201242804. Epub 2012 Dec 13.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Africa South of the Sahara
  • Bronchoalveolar Lavage
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / microbiology
  • CD8-Positive T-Lymphocytes / virology
  • Chemokine CCL4 / genetics
  • Chemokine CCL4 / immunology
  • Chemokine CCL5 / genetics
  • Chemokine CCL5 / immunology
  • Chemokines / biosynthesis*
  • Chemokines / genetics
  • Chemokines / immunology
  • Coinfection / genetics
  • Coinfection / immunology
  • Coinfection / microbiology
  • Coinfection / virology
  • Female
  • HIV Infections / immunology
  • HIV Infections / microbiology
  • HIV Infections / virology
  • HIV-1 / genetics
  • HIV-1 / immunology
  • HIV-1 / physiology*
  • Humans
  • Ligands
  • Lung / immunology
  • Lung / microbiology*
  • Lung / virology*
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis / immunology*
  • Receptors, CCR5 / genetics
  • Receptors, CCR5 / immunology
  • Receptors, Chemokine / biosynthesis*
  • Receptors, Chemokine / genetics
  • Receptors, Chemokine / immunology
  • Tuberculosis / genetics
  • Tuberculosis / immunology
  • Tuberculosis / microbiology
  • Tuberculosis / virology
  • Viral Load / genetics
  • Viral Load / immunology
  • Virus Replication / genetics*
  • Virus Replication / immunology
  • Young Adult

Substances

  • CCL5 protein, human
  • Chemokine CCL4
  • Chemokine CCL5
  • Chemokines
  • Ligands
  • Receptors, CCR5
  • Receptors, Chemokine