CONICET | Buscador de Institutos y Recursos Humanos

Cell mediated immunity, cytokines induced during the specific immune response and T cell populations are crucial factors for containing M. tuberculosis (Mtb) infection. Recent reports suggest a cross-regulation between adrenal steroids (glucocorticoids an dehidroepindrosterone, DHEA) and antigen-presenting cells (APC) function. Therefore, we investigated the role of adrenal hormones on the Mtb- induced dendritic cells (DC) functional capacity. To achieve this, we isolated monocytes from healthy donors peripheral blood by percoll gradients, differentiated them to DC by culturing monocytes with IL-4 and GM-CSF. Afterwards, we assessed i) the phenotype of DC after inducing their maturation overnight with Mtb in the presence or absence of cortisol (10-6M) or DHEA (10-7M) alone or in combination by flow cytometry and ii) the cytokines (IL-12, IL-10, TNFa) produced by DC after the mentioned culture conditions by ELISA. We observed, as expected, a significant increase on the expression of MHC-I, MHC-II, CD86 and CD83 (p< 0.05) and the production of IL-12, TNFa (p<0.05) and IL-10 (p<0.0001), after Mtb-stimulation. Cortisol treatment significantly inhibited the above mentioned Mtb-induced DCs functions. Interestingly, the presence of DHEA during the culture period enhanced the Mtb-induced expression of MHC I (p< 0.05), MHC II (p< 0.05), and CD86 (p<0.05), without affecting CD83 expression. Moreover, DHEA improved the production of IL-12 in response to Mtb stimulation (p<0.05), diminished the IL-10 secretion (p<0.05), and could not modify TNFa synthesis. a reversion of cortisols inhibitory effects by DHEA treatment. These data shows for the first time the relevance of the adrenal axis (especially of DHEA) in the modulation of DC function in the context of tuberculosis, a disease were the induction of a Th1 environment by APC is crucial for the development of an effective immune response to the mycobacteria

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