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HIV infection functionally impairs Mycobacterium tuberculosis-specific CD4 and CD8 T-cell responses

Amelio, Patrizia and Portevin, Damien and Hella, Jerry and Reither, Klaus and Kamwela, Lujeko and Lweno, Omar and Tumbo, Anneth and Geoffrey, Linda and Ohmiti, Khalid and Ding, Song and Pantaleo, Giuseppe and Daubenberger, Claudia and Perreau, Matthieu. (2019) HIV infection functionally impairs Mycobacterium tuberculosis-specific CD4 and CD8 T-cell responses. Journal of virology, 93 (5). e01728-18.

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Abstract

Human immunodeficiency virus (HIV) infection is the major risk factor predisposing for; Mycobacterium tuberculosis; progression from latent tuberculosis infection (LTBI) to tuberculosis disease (TB). Since long-term-treated aviremic HIV-infected individuals remained at higher risk of developing TB than HIV-uninfected individuals, we hypothesized that progression from LTBI to pulmonary TB (PTB) might be due not only to CD4 T-cell depletion but also to; M. tuberculosis; -specific CD4 T-cell functional impairment. To test this hypothesis,; M. tuberculosis; -specific T-cell frequencies and cytokine profiles were investigated in untreated Tanzanian individuals suffering from LTBI (; n; = 20) or PTB (; n; = 67) and compared to those of untreated; M. tuberculosis; /HIV-coinfected individuals suffering from LTBI (; n; = 15) or PTB (; n; = 10). We showed that HIV infection significantly reduced the proportion of Th2 (interleukin 4 [IL-4]/IL-5/IL-13) producing; M. tuberculosis; -specific CD4 T cells and IL-2-producing; M. tuberculosis; -specific CD4 and CD8 T cells in individuals with LTBI or PTB (; P < ; 0.05). Interestingly, the loss of IL-2 production was associated with a significant increase of PD-1 expression on; M. tuberculosis; -specific CD4 and CD8 T cells (; P < ; 0.05), while the loss of Th2 cytokine production was associated with a significant reduction of Gata-3 expression in memory CD4 T cells (; P < ; 0.05). Finally, we showed that the serum levels of IL-1α, IL-6, C-reactive protein (CRP), IL-23, and IP-10 were significantly reduced in; M. tuberculosis; /HIV-coinfected individuals with PTB compared to those in HIV-negative individuals with PTB (; P < ; 0.05), suggesting that HIV infection significantly suppresses; M. tuberculosis; -induced systemic proinflammatory cytokine responses. Taken together, this study suggests that in addition to depleting; M. tuberculosis; -specific CD4 T cells, HIV infection significantly impairs functionally favorable; M. tuberculosis; -specific CD4 T-cell responses in Tanzanian individuals with LTBI or PTB.; IMPORTANCE; Mycobacterium tuberculosis; and human immunodeficiency virus (HIV) infections are coendemic in several regions of the world, and; M. tuberculosis; /HIV-coinfected individuals are more susceptible to progression to tuberculosis disease. We therefore hypothesized that HIV infection would potentially impair; M. tuberculosis; -specific protective immunity in individuals suffering from latent tuberculosis infection (LTBI) or active pulmonary tuberculosis (PTB). In this study, we demonstrated that; M. tuberculosis; /HIV-coinfected individuals have fewer circulating; M. tuberculosis; -specific CD4 T cells and that those that remained were functionally impaired in both LTBI and PTB settings. In addition, we showed that HIV infection significantly interferes with; M. tuberculosis; -induced systemic proinflammatory cytokine/chemokine responses. Taken together, these data suggest that HIV infection impairs functionally favorable; M. tuberculosis; -specific immunity.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology > Clinical Immunology (Daubenberger)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Medicine > Clinical Research (Reither)
UniBasel Contributors:Portevin, Damien and Reither, Klaus and Tumbo, Anneth and Daubenberger, Claudia
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Society for Microbiology
ISSN:0022-538X
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:12 Mar 2019 09:56
Deposited On:12 Mar 2019 09:56

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