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.

中文翻译：

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PGE2在人类结核病中的免疫抑制作用

前列腺素E2（PGE2）是一种从花生四烯酸衍生的活性脂质化合物，可在几种病理学（例如慢性感染或癌症）中调节宿主免疫应答的不同阶段。有人提议操纵PGE2水平作为抵抗结核病（TB）的I型IFN信号的方法，但是在活动性TB患者中有关此途径的信息非常有限。在这里，我们证明了PGE2在人类宿主对结核分枝杆菌的免疫应答过程中发挥了强大的免疫抑制作用。因此，我们表明PGE 2抑制促炎细胞因子的淋巴增殖和细胞因子的产生，以及人类细胞中几种免疫受体表面表达的显着降低。然而，PGE2促进了抗原刺激的单核细胞的自噬通量，即使存在IFNα。以这种方式，由过度的免疫反应引起的炎症和免疫病理学的减轻成为有吸引力的治疗靶标。总之，我们的发现有助于了解PGE2介导的抗Mtb的知识，并突出了这种脂质介体作为改善抗结核治疗工具的潜力。