biostudies-literatureSchwartz LHHS | NIH | National Institute of Diabetes and Digestive and Kidney DiseasesOhio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research InstituteNIDDK NIH HHSHHS | NIH | Division of Loan RepaymentHHS | NIH | National Cancer InstituteOhio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (The James)NCI NIH HHSHHS | NIH | National Cancer Institute (NCI)HHS | NIH | Division of Loan Repayment (DLR)e2400666121https://www.ebi.ac.uk/biostudies/studies/S-EPMC11260129biostudies-literatureUnknown121(29)Urinary tract infection (UTI) commonly afflicts people with diabetes. This augmented infection risk is partly due to deregulated insulin receptor (IR) signaling in the kidney collecting duct. The collecting duct is composed of intercalated cells (ICs) and principal cells (PCs). Evidence suggests that ICs contribute to UTI defenses. Here, we interrogate how IR deletion in ICs impacts antibacterial defenses against uropathogenic <i>Escherichia coli.</i> We also explore how IR deletion affects immune responses in neighboring PCs with intact IR expression. To accomplish this objective, we profile the transcriptomes of IC and PC populations enriched from kidneys of wild-type and IC-specific IR knock-out mice that have increased UTI susceptibility. Transcriptomic analysis demonstrates that IR deProceedings of the National Academy of Sciences of the United States of AmericaInsulin receptor orchestrates kidney antibacterial defenses.PMC11260129P30 CA016058R01 DK114035R50 CA211524L40DK130152L40 DK130152R50CA211524R01 DK115737P30CA016058Vasquez Martinez GTurkoglu AYan PSpencer JDSalamon KSchwartz LSimoni AEichler TWang XZepeda-Orozco DfalseInsulin receptor orchestrates kidney antibacterial defenses.Urinary tract infection (UTI) commonly afflicts people with diabetes. This augmented infection risk is partly due to deregulated insulin receptor (IR) signaling in the kidney collecting duct. The collecting duct is composed of intercalated cells (ICs) and principal cells (PCs). Evidence suggests that ICs contribute to UTI defenses. Here, we interrogate how IR deletion in ICs impacts antibacterial defenses against uropathogenic <i>Escherichia coli.</i> We also explore how IR deletion affects immune responses in neighboring PCs with intact IR expression. To accomplish this objective, we profile the transcriptomes of IC and PC populations enriched from kidneys of wild-type and IC-specific IR knock-out mice that have increased UTI susceptibility. Transcriptomic analysis demonstrates that IR de2024-01-01T00:00:00Z2024 Jul2026-06-01T15:01:05.85Z2025-04-04T21:49:09.398ZS-EPMC112601293897673810.1073/pnas.2400666121