Relationship between chemokine receptor expression, chemokine levels and HIV-1 replication in the lungs of persons exposed to Mycobacterium tuberculosis
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Barbara Kalsdorf Keira H Skolimowska Thomas J Scriba Rod Dawson Keertan Dheda Kathryn Wood Jessica Hofmeister Willem A Hanekom Christoph Lange Robert WilkinsonAbstract
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.
Journal details
Journal European Journal of Immunology
Volume 43
Issue number 2
Pages 540-549
Publication date
Full text links
Publisher website (DOI) 10.1002/eji.201242804
Europe PubMed Central 23147374
Pubmed 23147374
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