DHEA induces autophagy in THP1-derived macrophages infected with Mycobacterium tuberculosis.

BONGIOVANNI BETTINA; MATA ESPINOSA DULCE; D'ATTILIO LUCIANO; LEÓN CONTRERAS JUAN CARLOS; MARQUEZ VELASCO RICARDO; BOTTASSO OSCAR; HERNANDEZ PANDO ROGELIO; BAY MARÍA LUISA

Medellin

Congreso; Immunocolombia 2015, 11º Congreso ALAI; 2015

Tuberculosis (TB) constitutes an important health problem today. In 2014, an estimated 8.6 million people developed TB and 1.3 million died from the disease (including 320 000 deaths among HIV-positive people). The number of TB deaths is unacceptably large given that most of them are preventable. The disease is caused by Mycobacterium tuberculosis (Mtb), a facultative intracellular bacterium that is capable of surviving and persisting within host mononuclear cells.In most cases, the immune response against Mtb is adequate and avoids the development of active disease. However, complete clearance of the pathogen is frequently not achieved. Mtb ensures its survival within host macrophages by arresting the maturation pathway that leads to phagosome?lysosome fusion, thus avoiding the phagolysosome that is rich in acid hydrolases capable of microbicidal degradation, and creating a suitable environment for bacillary survival and replication. As yet, while Mtb can block phagosome maturation, the induction of autophagy facilitates phagosome-lysosome fusion and bacilli clearance.Among modulators of the immune response hormones like adrenal and gonadal steroids, and neurotransmitters are known to play an influential role in this regard. Given our earlier studies in which adrenal steroids were found to modify the cellular immune responses from TB patients, it was sensible to analyze the immunomodulatory capability of cortisol and DHEA on macrophages infected with Mtb.In addressing this issue we have employed a model able to mimic the macrophage-Mtb interaction. Hence, we infected the human macrophage-like THP-1 cells with Mtb strain H37Rv and treated with Cortisol and DHEA at different doses. We monitored, cytokines gene expression and production, phagocytosis, intracellular-bacterial growth and autophagosoma formation. This approach provided new insight on the steroid hormones effects on the intracellular fate of Mtb. Cells were incubated in the presence or absence of Cortisol (10-6 M) and/or DHEA (10-6 M or 10-7 M) before Mtb (MOI 5:1).Mtb-infected cultures had increased amounts of TNF-α, sTNFR (soluble TNF receptor), IL1-β and IL10 respect the control group. Except for sTNFR levels, which were significantly higher in Cortisol-treated cultures, this hormone decreased TNF-α, IL1-β and IL-10 levels compared to infected cultures left without hormones (p