ROLE OF PGE2 ON NEUTROPHILS DURING HUMAN TUBERCULOSIS


Identification: Martin-Candela


Description

ROLE OF PGE2 ON NEUTROPHILS DURING HUMAN TUBERCULOSIS
Martin C 1;2 , Pellegrini JM 1;2 , Morelli MP 1;2 , Tateosian NL 1;2 , Amiano NO 1;2 , Ciallella L 3 ,Palmero DJ 3 , García VE 1;2 .

1 Departamento de Química Biológica. Facultad de Ciencias Exactas y Naturales. UBA, Intendente Güiraldes 2160, Pabellón II, 4°piso, Ciudad Universitaria (C1428EGA), Buenos Aires, Argentina.
2 Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN). Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires. Consejo Nacional de Investigaciones Científicas y Técnicas. Intendente Güiraldes 2160, Pabellón II, 4°piso, Ciudad Universitaria (C1428EGA), Buenos Aires, Argentina.
3 División Tisioneumonología Hospital F.J. Muñiz, Uspallata 2272, (C1282AEN) Buenos Aires, Argentina.

Tuberculosis (TB) is one of the top 10 causes of death worldwide. Prostaglandin E2 (PGE2), an active lipid compound derived from arachidonic acid, regulates different stages of the  response of the host during several pathologies such as chronic infections or cancer. Interestingly, manipulation of PGE2 levels was proposed as an approach for countering the Type I IFN signature of TB, although very limited information about this pathway in tuberculosis patients is available. Therefore, the aim of the present work was to investigate the role of this compound during human TB.
Neutrophils were obtained from heparinized peripheral blood from healthy donors (HD) and tuberculosis patients (TB) by Ficoll-Hypaque centrifugation and Dextran sedimentation. Cells were cultured (2x10ˆ6 cells/ml) with a Mycobacterium tuberculosis lysate (Mtb-Ag, 10μg/ml) with/without PGE2. Then, we evaluated the role of this lipidic mediator during the human immune response against Mtb-Ag by using flow cytometry and confocal microscopy assays. P-values <0,05 were considered significantly different.
Our results demonstrated that PGE2 exerts a immunosuppressive effect on neutrophil’s functions during the immune response of the human host against M. tuberculosis. In fact, we found that PGE2 significantly reduced the expression of several immunological receptors such as SLAMF1, CD11b and PD-L1 in neutrophils. Besides, neither Mtb-Ag nor PGE2 treatment modulated PD-L2 expression on human neutrophils.
On the other hand, PGE2 promoted autophagy in neutrophils cultured with Mtb antigens. Finally, we observed that PGE2 did not modify ROS production in Mtb-Ag stimulated neutrophils. These results suggest that PGE2 might attenuate the excessive inflammatory immune response caused by Mtb, emerging as an attractive therapeutic target. Together, our findings contribute to the knowledge of Mtb-resistance mediated by PGE2 and highlight the potential of this lipid mediator as a tool to improve anti-TB treatment.

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