RT Journal Article
SR Electronic
T1 Immunosuppressive role of PGE2 during human tuberculosis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.08.04.236257
DO 10.1101/2020.08.04.236257
A1 Joaquín Miguel Pellegrini
A1 Nancy Liliana Tateosian
A1 María Paula Morelli
A1 Agustín Rollandelli
A1 Nicolás Oscar Amiano
A1 Domingo Palmero
A1 Alberto Levi
A1 Lorena Ciallella
A1 María Isabel Colombo
A1 Verónica Edith García
YR 2020
UL http://biorxiv.org/content/early/2020/08/05/2020.08.04.236257.abstract
AB Prostaglandin E2 (PGE2), an active lipid compound derived from arachidonic acid, regulates different stages of the immune response of the host during several pathologies such as chronic infections or cancer. Manipulation of PGE2 levels was proposed as an approach for countering the Type I IFN signature of tuberculosis (TB), but very limited information exists about this pathway in patients with active TB. Here, we demonstrated that PGE2 exerts a potent immunosuppressive action during the immune response of the human host against M. tuberculosis. Thus, we showed that PGE2 inhibited both lymphoproliferation and cytokine production of proinflammatory cytokines, together with a significant reduction of the surface expression of several immunological receptors in human cells. However, PGE2 promoted the autophagic flux of antigen-stimulated monocytes, even in the presence of IFNα. In this way, the attenuation of inflammation and immunopathology caused by an excessive immune response emerges 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.Competing Interest StatementThe authors have declared no competing interest.