ROLE OF PROSTAGLANDIN E2 DURING THE HUMAN IMMUNE RESPONSE AGAINST Mycobacterium tuberculosis

DOMINGO J. PALMERO; CASTELLO, FLORENCIA A.; ROLANDELLI AGUSTIN; GARCÍA V.E; ALBERTO LEVI; MARIA PAULA MORELLI; JOAQUIN PELLEGRINI; CASCO, NICOLÁS; AMIANO NICOLAS; N. TATEOSIAN

Workshop; Workshop ?Buenos Aires research conferences on autophagy. Molecular mechanisms in biology and diseases; 2017

Tuberculosis (TB) is, alongside HIV, the leading cause of death from an infectious disease. In fact, Mycobacterium tuberculosis (Mtb)causes nearly 10 million of new cases and 1.5 million deaths per year. Prostaglandin E2 (PGE2), an active lipid compound derived fromarachidonic acid, is a key mediator of immunopathology in chronic infections and cancer by regulating different stages of immuneresponses. Manipulation of PGE2 levels was proposed as an approach for countering the Type I IFN signature of TB patients and toalleviate active TB disease, but very limited information exists about this pathway in patients with active TB and the role of autophagy,a cellular process involved in defense mechanism against Mtb. Here we investigated the role of PGE2 on modulation of humanimmune responses against Mtb. First, we analyzed the expression of surface molecules that play an important role on T cell activation.Peripheral blood mononuclear cells from healthy donors (HD) and TB patients were cultivated for 16 h without stimulus to allowmonocyte adherence. Cells were then stimulated with Mtb-Ag ± PGE2 (2 μg/ml) for 24 h or 5 days. Flow cytometry (FC) analysisrevealed that PGE2 significantly reduced SLAM and CD31 expression on CD3+ T lymphocytes and CD80 and MHCI expression onCD14+ monocytes from all groups under study. Interestingly, PGE2 reduced the lymphocytes proliferation from HD and TB patients.Besides, autophagy levels were analyzed by FC and Confocal Microscopy against LC3B-II. We found that PGE2 significantly increasedLC3 puncta accumulation on monocytes from HD and TB patients. Finally, we observed an interesting increase in apoptotic blebsformation in cells treated with PGE2. Taken together, PGE2 has immunomodulatory features in both innate and adaptive immuneresponses during human TB. Our findings might contribute to deepen the mechanisms that operate on Mtb-resistance mediated byPGE2 and the potential of PGE2 as a tool to improve anti-TB treatment.