Abstract
BackgroundMycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB), affecting approximately one third of the world’s population. Development of an adequate immune response will determine disease progression or progress to chronic infection. Risk of developing TB among human immunodeficiency virus (HIV)-coinfected patients (HIV-TB) is 20–30 times higher than those without HIV infection, and a synergistic interplay between these two pathogens accelerates the decline in immunological functions. TB treatment in HIV-TB coinfected persons is challenging and it has a prolonged duration, mainly due to the immune system failure to provide an adequate support for the therapy. Therefore, we aimed to study the role of the hormone 7-oxo-dehydroepiandrosterone (7-OD) as a modulator of anti-tuberculosis immune responses in the context of HIV-TB coinfection.MethodsA cross-sectional study was conducted among HIV-TB patients and healthy donors (HD). We characterized the ex vivo phenotype of CD4 + T cells and also evaluated in vitro antigen-specific responses by Mtb stimulation of peripheral blood mononuclear cells (PBMCs) in the presence or absence of 7-OD. We assessed lymphoproliferative activity, cytokine production and master transcription factor profiles.ResultsOur results show that HIV-TB patients were not able to generate successful anti-tubercular responses in vitro compared to HD, as reduced IFN-γ/IL-10 and IFN-γ/IL-17A ratios were observed. Interestingly, treatment with 7-OD enhanced Th1 responses by increasing Mtb-induced proliferation and the production of IFN-γ and TNF-α over IL-10 levels. Additionally, in vitro Mtb stimulation augmented the frequency of cells with a regulatory phenotype, while 7-OD reduced the proportion of these subsets and induced an increase in CD4 + T-bet+ (Th1) subpopulation, which is associated with clinical data linked to an improved disease outcome.ConclusionsWe conclude that 7-OD modifies the cytokine balance and the phenotype of CD4 + T cells towards a more favorable profile for mycobacteria control. These results provide new data to delineate novel treatment approaches as co-adjuvant for the treatment of TB.
Highlights
Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB), affecting approximately one third of the world’s population
These data suggest that human immunodeficiency virus (HIV)-TB patients are not able to generate an adequate response for the containment of the bacteria, as a result of the reduction in IFN-γ/IL-10 and IFN-γ/IL-17A ratios
peripheral blood mononuclear cells (PBMCs) from healthy donors (HD) and HIV and Mycobacterium tuberculosis (HIV-TB) individuals were stimulated with gammairradiated Mtb (10 μg/ml) for 5 days
Summary
Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB), affecting approximately one third of the world’s population. Highly active antiretroviral therapy impedes HIV replication and leads to increased CD4 + T cell numbers, Mtb-specific responses do not change substantially over the first six months on antiretroviral therapy [1]. This situation unravels the need for developing additional immunotherapies to protect from and control Mtb infection, especially in HIV+ individuals. In the context of HIV-TB coinfection, these treatments should aim to enhance antigen-specific immune responses, reduce excess inflammation, preserve cell function or improve the effectiveness of conventional therapies. HDT could offer additional advantages for coinfected patients since they may reduce the length of treatments, achieving better outcomes and/or decreasing the chances of relapse or reinfection [2, 3]
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