RESUMO
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-1ß 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.
Assuntos
Quimiocinas/biossíntese , HIV-1/fisiologia , Pulmão/microbiologia , Pulmão/virologia , Mycobacterium tuberculosis/imunologia , Receptores de Quimiocinas/biossíntese , Replicação Viral/genética , Adulto , África Subsaariana , Lavagem Broncoalveolar , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/microbiologia , Linfócitos T CD8-Positivos/virologia , Quimiocina CCL4/genética , Quimiocina CCL4/imunologia , Quimiocina CCL5/genética , Quimiocina CCL5/imunologia , Quimiocinas/genética , Quimiocinas/imunologia , Coinfecção/genética , Coinfecção/imunologia , Coinfecção/microbiologia , Coinfecção/virologia , Feminino , Infecções por HIV/imunologia , Infecções por HIV/microbiologia , Infecções por HIV/virologia , HIV-1/genética , HIV-1/imunologia , Humanos , Ligantes , Pulmão/imunologia , Masculino , Pessoa de Meia-Idade , Receptores CCR5/genética , Receptores CCR5/imunologia , Receptores de Quimiocinas/genética , Receptores de Quimiocinas/imunologia , Tuberculose/genética , Tuberculose/imunologia , Tuberculose/microbiologia , Tuberculose/virologia , Carga Viral/genética , Carga Viral/imunologia , Replicação Viral/imunologia , Adulto JovemRESUMO
We investigated whether the proinflammatory T cell cytokines IL-17 and IL-22 are induced by human mycobacterial infection. Remarkably, >20% of specific cytokine-producing CD4(+) T cells in peripheral blood of healthy, mycobacteria-exposed adults expressed IL-17 or IL-22. Specific IL-17- and IL-22-producing CD4(+) T cells were distinct from each other and from Th1 cytokine-producing cells. These cells had phenotypic characteristics of long-lived central memory cells. In patients with tuberculosis disease, peripheral blood frequencies of these cells were reduced, whereas bronchoalveolar lavage fluid contained higher levels of IL-22 protein compared with healthy controls. IL-17 was not detected in this fluid, which may be due to suppression by Th1 cytokines, as PBMC IL-17 production was inhibited by IFN-gamma in vitro. However, Th1 cytokines had no effect on IL-22 production in vitro. Our results imply that the magnitude and complexity of the anti-mycobacterial immune response have historically been underestimated. IL-17- and IL-22-producing CD4(+) T cells may play important roles in the human immune response to mycobacteria.