Browsing by Author "Mesch, Viviana"

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    Determination of dehydroepiandrosterone and its biologically active oxygenated metabolites in human plasma evinces a hormonal imbalance during HIV-TB coinfection
    (2018-04-27) Vecchione, María Belén; Eiras, Javier; Suarez, Guadalupe Verónica; Angerami, Matías Tomás; Marquez, Cecilia; Sued, Omar; Ben, Graciela; Pérez, Héctor Miguel; Gonzalez, Diego; Maidana, Patricia; Mesch, Viviana; Quiroga, María Florencia; Bruttomesso, Andrea Claudia
    An estimated one third of the world’s population is affected by latent tuberculosis (TB), which once active represents a leading cause of death among infectious diseases. Human immunodeficiency virus (HIV) infection is a main predisposing factor to TB reactivation. Individuals HIV-TB co-infected develop a chronic state of inflammation associated with hypothalamic-pituitary-adrenal (HPA) axis dysregulation. This results in a hormonal imbalance, disturbing the physiological levels of cortisol and dehydroepiandrosterone (DHEA). DHEA and its oxygenated metabolites androstenediol (AED), androstenetriol (AET) and 7-oxo-DHEA are immunomodulatory compounds that may regulate physiopathology in HIV-TB co-infection. In order to study possible changes in plasma levels of these hormones, we developed an approach based on high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). To our knowledge, this represents the first report of their simultaneous measurement in HIV-TB individuals and the comparison with healthy donors, obtaining statistically higher plasma levels of DHEA, AET and 7-oxo-DHEA in patients. Moreover, we found that concentrations of 7-oxo-DHEA positively correlated with absolute CD4+ T cell counts, nadir CD4+ T cell values and with individuals who presented TB restricted to the lungs. This research contributes to understanding the role of these hormones in HIV-TB and emphasizes the importance of deepening their study in this context.
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    HIV-TB co-infection impairs CD8+ T-cell differentiation and function while dehydroepiandrosterone improves cytotoxic anti-tubercular immune responses
    (2015-9) Suarez, Guadalupe V.; Angerami, Matias; Vecchione, María B.; Laufer, Natalia; Turk, Gabriela; Ruiz, Maria; Mesch, Viviana; Fabre, Bibiana; Maidana, Patricia; Ameri, Diego; Cahn, Pedro; Sued, Omar; Salomon, Horacio; Bottasso, Oscar A.; Quiroga, María F.
    Tuberculosis (TB) is the leading cause of death among HIV-positive patients. The decreasing frequencies of terminal effector (TTE) CD8+T cells may increase reactivation risk in persons latently infected with Mycobacterium tuberculosis (Mtb). We have previously shown that dehydroepiandrosterone (DHEA) increases the protective antitubercular immune responses in HIV–TB patients. Here, we aimed to study Mtb-specific cytotoxicity, IFN-γ secretion, memory status of CD8+T cells, and their modulation by DHEA during HIV–TB coinfection. CD8+T cells from HIV–TB patients showed a more differentiated phenotype with diminished naïve and higher effector memory and TTE T-cell frequencies compared to healthy donors both in total and Mtb-specific CD8+T cells. Notably, CD8+T cells from HIV–TB patients displayed higher Terminal Effector (TTE) CD45RAdim proportions with lower CD45RA expression levels, suggesting a not fully differentiated phenotype. Also, PD-1 expression levels on CD8+T cells from HIV–TB patients increased although restricted to the CD27+ population. Interestingly, DHEA plasma levels positively correlated with TTE in CD8+T cells and in vitro DHEA treatment enhanced Mtb-specific cytotoxic responses and terminal differentiation in CD8+T cells from HIV–TB patients. Our data suggest that HIV–TB coinfection promotes a deficient CD8+ T-cell differentiation, whereas DHEA may contribute to improving antitubercular immunity by enhancing CD8+T-cell functions during HIV–TB coinfection.
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    Immune variations throughout the course of tuberculosis treatment and its relationship with adrenal hormone changes in HIV-1 patients co-infected with Mycobacterium tuberculosis
    (2022-03) Vecchione, María Belén; Angerami, Matias; Suarez, Guadalupe Verónica; Turk, Gabriela; Laufer, Natalia; Ben, Graciela; Ameri, Diego; Gonzalez, Diego; Parodi, Laura M.; Giavedoni, Luis D.; Maidana, Patricia; Fabre, Bibiana; Mesch, Viviana; Sued, Omar; Quiroga, Maria Florencia
    HIV infection is a major risk factor predisposing for Mycobacterium tuberculosis infection and progression to active tuberculosis (TB). As host immune response defines the course of infection, we aimed to identify immuno-endocrine changes over six-months of anti-TB chemotherapy in HIV+ people. Plasma levels of cortisol, DHEA and DHEA-S, percentages of CD4+ regulatory T cell subsets and number of IFN-γ-secreting cells were determined. Several cytokines, chemokines and C-reactive protein levels were measured. Results were correlated with clinical parameters as predictors of infection resolution and compared to similar data from HIV+ individuals, HIV-infected persons with latent TB infection and healthy donors. Throughout the course of anti-TB/HIV treatment, DHEA and DHEA-S plasma levels raised while cortisol diminished, which correlated to predictive factors of infection resolution. Furthermore, the balance between cortisol and DHEA, together with clinical assessment, may be considered as an indicator of clinical outcome after anti-TB treatment in HIV+ individuals. Clinical improvement was associated with reduced frequency of unconventional Tregs, increment in IFN-γ-secreting cells, diminution of systemic inflammation and changes of circulating cytokines and chemokines. This study suggests that the combined anti-HIV/TB therapies result in partial restoration of both, immune function and adrenal hormone plasma levels.