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

GARCIA, VE; LEVI, A; MORELLI, MARÍA P.; PELLEGRINI, J; PALMERO, D; CASTELLO, FA; ROLANDELLI, A; CASCO, N; AMIANO, N; TATEOSIAN, NANCY L.

Conferencia; Buenos Aires research conferences on autophagy; 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 from arachidonic acid, is a key mediator of immunopathology in chronic infections and cancer by regulating different stages of immune responses. Manipulation of PGE2 levels was proposed as an approach for countering the Type I IFN signature of TB patients and to alleviate 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 human immune 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 allow monocyte adherence. Cells were then stimulated with Mtb-Ag ± PGE2 (2 µg/ml) for 24 h or 5 days. Flow cytometry (FC) analysis revealed that PGE2 significantly reduced SLAM and CD31 expression on CD3+ T lymphocytes and CD80 and MHCI expression on CD14+ 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 increased LC3 puncta accumulation on monocytes from HD and TB patients. Finally, we observed an interesting increase in apoptotic blebs formation in cells treated with PGE2. Taken together, PGE2 has immunomodulatory features in both innate and adaptive immune responses during human TB. Our findings might contribute to deepen the mechanisms that operate on Mtb-resistance mediated by PGE2 and the potential of PGE2 as a tool to improve anti-TB treatment.