Pseudomonas aeruginosa is a severe Gram-negative opportunistic bacterium that causes a spectrum of organ system diseases, particularly in immunocompromised patients. This bacterium has been shown to induce unfolded protein response (UPR) during mammalian infection. Annexin A2 (AnxA2) is a multicompartmental protein relating to a number of cellular processes; however, it remains unknown whether AnxA2 coordinates a UPR pathway under bacterial infection conditions. Here, we report that the endoplasmic reticulum stress inositol-requiring enzyme 1 (IRE1)–X-box binding protein 1 (XBP1) pathway was up-regulated by AnxA2 through p38 MAPK signaling following P. aeruginosa infection in macrophages, whereas ATF4 and ATF6 not. In addition, XBP1 was found as a positive regulator of innate immunity to tame P. aeruginosa challenges by enhancing autophagy and bacterial clearance. XBP1 also facilitated NF-κB activation to elicit the release of proinflammatory cytokines predominantly in macrophages. Together, our findings identify AnxA2 as a regulator for XBP1-mediated UPR pathway.

中文翻译：

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膜联蛋白 A2 在铜绿假单胞菌感染期间通过巨噬细胞中的 IRE1-XBP1 轴调节未折叠蛋白反应

铜绿假单胞菌是一种严重的革兰氏阴性机会性细菌，可引起一系列器官系统疾病，尤其是在免疫功能低下的患者中。这种细菌已被证明在哺乳动物感染期间诱导未折叠蛋白反应 (UPR)。膜联蛋白 A2 (AnxA2) 是一种与许多细胞过程相关的多室蛋白；然而，尚不清楚 AnxA2 是否在细菌感染条件下协调 UPR 途径。在这里，我们报告在巨噬细胞中铜绿假单胞菌感染后，AnxA2 通过 p38 MAPK 信号通路上调内质网应激肌醇需要酶 1 (IRE1)-X-box 结合蛋白 1 (XBP1) 通路，而 ATF4 和 ATF6不是。此外，XBP1 被发现是驯服先天免疫的正调节因子铜绿假单胞菌通过增强自噬和细菌清除来挑战。XBP1 还促进了 NF-κB 的激活，以引发主要在巨噬细胞中释放促炎细胞因子。总之，我们的研究结果将 AnxA2 确定为 XBP1 介导的 UPR 通路的调节剂。