Modulation of the phenotype and function of Mycobacterium tuberculosis-stimulated dendritic cells by adrenal steroids

ANGERAMI M; SUAREZ G; PASCUTTI MF; SALOMON H; BOTTASSO O; QUIROGA MF

INTERNATIONAL IMMUNOLOGY

OXFORD UNIV PRESS

Lugar: Tokio; Año: 2013 vol. 25 p. 405 - 411

0953-8178

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 cell?s (DC) functional capacity.  Studies included: the phenotype after inducing DC?s maturation with Mtb in the presence or absence of cortisol or DHEA alone or in combination; the cytokines (IL-12, IL-10, TNF-a) produced by DC after the mentioned culture conditions; and the proliferation and IFN-g production displayed by T cell after co-culture DC loaded with Mtb in the presence of DHEA.  Cortisol significantly inhibited Mtb-induced DC?s functions. Interestingly, the presence of DHEA enhanced the Mtb-induced expression of MHC I, MHC II and CD86 and increased ERK1/2 phosphorylation. Also, DHEA improved the production of IL-12 in response to Mtb stimulation, diminished the IL-10 secretion, and could not modify TNF-a synthesis.  Importantly, we observed that DHEA enhanced the antigen-specific T cell proliferation and IFN-g production induced by Mtb-stimulated dendritic cells.  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.