biostudies-literaturePandey ANIAID NIH HHSNational Natural Science Foundation of China103https://www.ebi.ac.uk/biostudies/studies/S-EPMC5919948biostudies-literatureUnknown8<i>Brucella</i> spp. are intracellular vacuolar pathogens that causes brucellosis, a worldwide zoonosis of profound importance. We previously demonstrated that the activity of host unfolded protein response (UPR) sensor IRE1α (inositol-requiring enzyme 1) and ER-associated autophagy confer susceptibility to <i>Brucella melitensis</i> and <i>Brucella abortus</i> intracellular replication. However, the mechanism by which host IRE1α regulates the pathogen intracellular lifestyle remains elusive. In this study, by employing a diverse array of molecular approaches, including biochemical analyses, fluorescence microscopy imaging, and infection assays using primary cells derived from <i>Ern1</i> (encoding IRE1) conditional knockout mice, we address this gap in our understanding by demonstrating tFrontiers in cellular and infection microbiologyActivation of Host IRE1α-Dependent Signaling Axis Contributes the Intracellular Parasitism of <i>Brucella melitensis</i>.PMC5919948R01 AI04849681371773U54 AI057156R21 AI072446Cabello ALZhang MZde Figueiredo PQin QMFeng XLin FFeng HQIwawaki TPandey ARice-Ficht AFicht TAda Costa LFfalseActivation of Host IRE1α-Dependent Signaling Axis Contributes the Intracellular Parasitism of <i>Brucella melitensis</i>.<i>Brucella</i> spp. are intracellular vacuolar pathogens that causes brucellosis, a worldwide zoonosis of profound importance. We previously demonstrated that the activity of host unfolded protein response (UPR) sensor IRE1α (inositol-requiring enzyme 1) and ER-associated autophagy confer susceptibility to <i>Brucella melitensis</i> and <i>Brucella abortus</i> intracellular replication. However, the mechanism by which host IRE1α regulates the pathogen intracellular lifestyle remains elusive. In this study, by employing a diverse array of molecular approaches, including biochemical analyses, fluorescence microscopy imaging, and infection assays using primary cells derived from <i>Ern1</i> (encoding IRE1) conditional knockout mice, we address this gap in our understanding by demonstrating t2018-01-01T00:00:00Z20182025-05-31T22:41:28.15Z2025-05-31T22:41:28.15ZS-EPMC59199482973232010.3389/fcimb.2018.00103