title: Relationship between chemokine receptor expression, chemokine levels and HIV-1 replication in the lungs of persons exposed to Mycobacterium tuberculosis.
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.
authors.affiliation: Clinical Infectious Diseases Research Initiative, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Observatory, Cape Town, South Africa. bkalsdorf@fz-borstel.de
authors.forename: Barbara
authors.initials: B
authors.lastname: Kalsdorf
authors.forename: Keira H
authors.initials: KH
authors.lastname: Skolimowska
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Scriba
authors.forename: Rod
authors.initials: R
authors.lastname: Dawson
authors.forename: Keertan
authors.initials: K
authors.lastname: Dheda
authors.forename: Kathryn
authors.initials: K
authors.lastname: Wood
authors.forename: Jessica
authors.initials: J
authors.lastname: Hofmeister
authors.forename: Willem A
authors.initials: WA
authors.lastname: Hanekom
authors.forename: Christoph
authors.initials: C
authors.lastname: Lange
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Wilkinson
mesh_terms: D000328:Adult; D017954:Africa South of the Sahara; D018893:Bronchoalveolar Lavage; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000382:microbiology / Q000821:virology; D054407:Chemokine CCL4 / Q000235:genetics / Q000276:immunology; D018946:Chemokine CCL5 / Q000235:genetics / Q000276:immunology; D018925:Chemokines / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D060085:Coinfection / Q000235:genetics / Q000276:immunology / Q000382:microbiology / Q000821:virology; D005260:Female; D015658:HIV Infections / Q000276:immunology / Q000382:microbiology / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D006801:Humans; D008024:Ligands; D008168:Lung / Q000276:immunology / Q000382:microbiology* / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D019713:Receptors, CCR5 / Q000235:genetics / Q000276:immunology; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D014376:Tuberculosis / Q000235:genetics / Q000276:immunology / Q000382:microbiology / Q000821:virology; D019562:Viral Load / Q000235:genetics / Q000276:immunology; D014779:Virus Replication / Q000235:genetics* / Q000276:immunology; D055815:Young Adult
chemical_list: C483024:CCL5 protein, human; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D018925:Chemokines; D008024:Ligands; D019713:Receptors, CCR5; D019707:Receptors, Chemokine