1. Relationship Between HIV Coinfection, Interleukin 10 Production, and Mycobacterium tuberculosis in Human Lymph Node Granulomas.
- Author
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Diedrich CR, O'Hern J, Gutierrez MG, Allie N, Papier P, Meintjes G, Coussens AK, Wainwright H, and Wilkinson RJ
- Subjects
- Adult, Aged, CD4 Lymphocyte Count methods, CD4-Positive T-Lymphocytes metabolism, CD4-Positive T-Lymphocytes microbiology, CD4-Positive T-Lymphocytes virology, CD8-Positive T-Lymphocytes metabolism, CD8-Positive T-Lymphocytes microbiology, CD8-Positive T-Lymphocytes virology, Coinfection microbiology, Coinfection virology, Female, Granuloma microbiology, Granuloma virology, HIV Infections microbiology, HIV Infections virology, HIV-1 pathogenicity, Humans, Interferon-gamma metabolism, Lymph Nodes microbiology, Lymph Nodes virology, Male, Middle Aged, Mycobacterium tuberculosis pathogenicity, Tuberculosis microbiology, Tuberculosis virology, Young Adult, Coinfection metabolism, Granuloma metabolism, HIV Infections metabolism, Interleukin-10 metabolism, Lymph Nodes metabolism, Tuberculosis metabolism
- Abstract
Background: Human immunodeficiency virus type 1 (HIV)-infected persons are more susceptible to tuberculosis than HIV-uninfected persons. Low peripheral CD4
+ T-cell count is not the sole cause of higher susceptibility, because HIV-infected persons with a high peripheral CD4+ T-cell count and those prescribed successful antiretroviral therapy (ART) remain more prone to active tuberculosis than HIV-uninfected persons. We hypothesized that the increase in susceptibility is caused by the ability of HIV to manipulate Mycobacterium tuberculosis-associated granulomas., Methods: We examined 71 excised cervical lymph nodes (LNs) from persons with HIV and M. tuberculosis coinfection, those with HIV monoinfection, and those with M. tuberculosis monoinfection with a spectrum of peripheral CD4+ T-cell counts and ART statuses. We quantified differences in M. tuberculosis levels, HIV p24 levels, cellular response, and cytokine presence within granulomas., Results: HIV increased M. tuberculosis numbers and reduced CD4+ T-cell counts within granulomas. Peripheral CD4+ T-cell depletion correlated with granulomas that contained fewer CD4+ and CD8+ T cells, less interferon γ, more neutrophils, more interleukin 10 (IL-10), and increased M. tuberculosis numbers. M. tuberculosis numbers correlated positively with IL-10 and interferon α levels and fewer CD4+ and CD8+ T cells. ART reduced IL-10 production., Conclusions: Peripheral CD4+ T-cell depletion correlated with increased M. tuberculosis presence, increased IL-10 production, and other phenotypic changes within granulomas, demonstrating the HIV infection progressively changes these granulomas., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.)- Published
- 2016
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