biostudies-literatureZhou CMNIAID NIH HHSNIGMS NIH HHS375-384https://www.ebi.ac.uk/biostudies/studies/S-EPMC8669835biostudies-literatureUnknown110(2)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 tJournal of leukocyte biologyAnnexin A2 regulates unfolded protein response via IRE1-XBP1 axis in macrophages during P. aeruginosa infection.PMC8669835R01 AI109317P20 GM103442R01 AI138203P20 GM113123Pu QLin PWu MWang BWu QZhou CMYu XJLuo LMQin SfalseAnnexin A2 regulates unfolded protein response via IRE1-XBP1 axis in macrophages during P. aeruginosa infection.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 t2021-01-01T00:00:00Z2021 Aug2025-04-04T19:40:23.747Z2025-04-04T19:40:23.747ZS-EPMC86698353322553610.1002/jlb.3a1219-686rr10.1002/JLB.3A1219-686RR