Functional modulation by cortisol and/or DHEA on THP1-derived macrophages infected with Mycobacterium tuberculosis

BONGIOVANNI B; ESPINOSA DULCE M; MARQUEZ VELASCO R; BOTTASSO O; HERNANDEZ PANDO R; BAY ML

Milán

Congreso; 15th International Congress of Immunology, Milán 22-27 Agosto 2013 (Abstract P4.05.11).; 2013

IUIS

Tuberculosis (TB) is an ancient disease caused by the intracellular pathogen Mycobacterium tuberculosis (Mtb).  Partly because macrophages play a central role in the response against Mtb and our previous work indicating an unbalanced immune-endocrine response in TB patients, we have now studied whether cortisol and dehydroepiandrosterone (DHEA) were likely to modify the macrophage response upon infection with Mtb. Macrophages derived from THP-1 monocytic cell line were exposed to live Mtb strain H37Rv (MOI 5:1) during 3 hours in the presence or absence of cortisol (1 μM) and/or DHEA (1 and 0.1μM). Upon washing, cells were cultured for 1 (T0), 24 (T1) and 96 hours (T2) in the same media with or without hormones. End points included: phagocytic capacity (T0); cytokine levels in macrophage culture supernatants (TNF-a, IL-1B, IL-6, TGF-B and IL-10, T1), and number of CFU in agar-Middlebrook media exposed to lysed macrophages which had been cultured as mentioned (T0, T1 and T2). Single cortisol-treated cultures had a decreased Mtb phagocytosis respect to untreated counterparts (p<0.05). Cortisol, alone or combined with DHEA, inhibited the Mtb-induced production of TNF-a, IL-1B and IL-10 (p<0.05). A time-related rise in CFU was seen in control cultures (p<0.05) whereas treatment with cortisol and DHEA resulted in an inverse trend (p<0.05). Combined treatment with cortisol and DHEA seems to favor the macrophage effector response, in the sense of bacillary growth control, apparently in no close correspondence with the profile of cytokines involved in such regard.