Annexin A2 regulates unfolded protein response via IRE1–XBP1 axis in macrophages during<i>P. aeruginosa</i>infection
Chuan‐Min Zhou, Limei Luo, Ping Lin, Qinqin Pu, Biao Wang, Shugang Qin, Qun Wu, Xue-jie Yu, Min Wu
Abstract
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.