To date, the implications of prostaglandin I2 (PGI₂), a prominent lipid mediator for modulation of immune responses, has not been clearly understood in Brucella infection. In this study, we found that cyclooxygenase-2 (COX-2) was significantly expressed in both infected bone marrow-derived macrophages (BMMs) and RAW 264.7 cells. Prostaglandin I2 synthase (PTGIS) expression was not significantly changed, and PGI₂ receptor (PTGIR) expression was downregulated in BMMs but upregulated in RAW 264.7 macrophages at late infection. Here, we presented that PGI₂, a COX-derived metabolite, was produced by macrophages during Brucella infection and its production was regulated by COX-2 and IL-10. We suggested that PGI₂ and selexipag, a potent PGI₂ analogue, inhibited Brucella internalization through IP signaling which led to down-regulation of F-actin polymerization and p38α MAPK activity. Administration with selexipag suppressed immune responses and resulted in a notable reduction in bacterial burden in spleen of Brucella-challenged mice. Taken together, our study is the first to characterize PGI₂ synthesis and its effect in evasion strategy of macrophages against Brucella infection.

迄今为止，前列腺素 I2 (PGI ₂ ) 是一种用于调节免疫反应的重要脂质介质，其在布鲁氏菌感染中的作用尚未明确。在这项研究中，我们发现cyclooxygenase-2 ( COX-2 ) 在受感染的骨髓衍生巨噬细胞 (BMM) 和 RAW 264.7 细胞中均显着表达。前列腺素 I2 合酶( PTGIS ) 表达没有显着变化，PGI ₂ 受体( PTGIR ) 表达在 BMM 中下调，但在感染晚期 RAW 264.7 巨噬细胞中上调。在这里，我们介绍了 PGI ₂是一种 COX 衍生代谢物，在布鲁氏菌感染期间由巨噬细胞产生，其产生受 COX-2 和 IL-10 的调节。我们建议 PGI ₂和 selexipag（一种有效的 PGI ₂类似物）通过 IP 信号传导抑制布鲁氏菌内化，从而导致 F-肌动蛋白聚合和 p38α MAPK 活性的下调。服用司来帕格可抑制免疫反应，并导致布鲁氏菌攻击小鼠脾脏中的细菌负荷显着降低。总之，我们的研究首次描述了 PGI ₂合成及其在巨噬细胞对布鲁氏菌感染的逃避策略中的作用。