MP25-09 MICROBIAL EXPOSURE REDUCES SUSCEPTIBILITY TO LOCALIZED UROPATHOGENIC E. COLI INFECTION IN THE BLADDER AND UROSEPSIS

Abstract

You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder I (MP25)1 Sep 2021MP25-09 MICROBIAL EXPOSURE REDUCES SUSCEPTIBILITY TO LOCALIZED UROPATHOGENIC E. COLI INFECTION IN THE BLADDER AND UROSEPSIS Matthew Martin, Whitney Swanson, Tamara Kucaba, Molly Ingersoll, and Tom Griffith Matthew MartinMatthew Martin More articles by this author , Whitney SwansonWhitney Swanson More articles by this author , Tamara KucabaTamara Kucaba More articles by this author , Molly IngersollMolly Ingersoll More articles by this author , and Tom GriffithTom Griffith More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002022.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Urinary tract infections (UTI) are the most prevalent infectious disease of the bladder-affecting >130 million people worldwide annually. Uropathogenic E. coli (UPEC) causes most UTI, starting with bladder colonization and then ascension to the kidneys. In severe cases of pyelonephritis, bacteria can enter the bloodstream, causing urosepsis. The immune system is involved in the development of these pathologies and response to treatment, but relatively little is known about how the basal state of the immune system influences the ability to respond to local or systemic UPEC infection. The difficulty in performing hypothesis-driven research in humans justifies the need for a clinically relevant experimental UTI/urosepsis model. Most preclinical studies are conducted with specific pathogen-free (SPF) mice, which possess a largely naïve immune system equivalent to neonatal humans. Cohousing (CoH) SPF mice with microbially diverse pet store mice matures the immune system to resemble that of adult humans. Therefore, the objective of these studies is to determine how prior microbial exposure affects the immune response to local and systemic UPEC infections. METHODS: For these studies, we infected SPF and CoH mice with UPEC strain UTI89 locally via bladder instillation or systemically via intravenous injection. Immune cell composition in the bladder was determined before and after infection, and bacterial clearance and survival following infection was monitored. RESULTS: Microbial exposure altered the baseline immune cell composition in the bladder, with CoH mice showing increased numbers of CD4 T cells and neutrophils. Interestingly, CoH mice were better able to clear UPEC infection following local infection of the bladder. Following systemic infection to model urosepsis, greater numbers of immune cells (especially neutrophils) were found in the circulation of CoH mice, and CoH mice showed faster clearance of infection in the blood, spleen, and kidney. Importantly, all SPF mice succumbed to infection within 48 hours, while all CoH mice survived beyond 72 hours. CONCLUSIONS: Our results have important implications for models of UTI/urosepsis. They suggest a general history of microbial exposure reduces susceptibility to localized bladder infection and urosepsis. While these studies importantly further our understanding of the immune response initiated after local or systemic UPEC infection, they also suggest mouse studies incorporating exposure to diverse infections may provide a more clinically relevant experimental UTI/urosepsis model. Source of Funding: American Urological Association Research Scholar AwardUniversity of Minnesota Department of Urology General Research Funds © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e456-e456 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Matthew Martin More articles by this author Whitney Swanson More articles by this author Tamara Kucaba More articles by this author Molly Ingersoll More articles by this author Tom Griffith More articles by this author Expand All Advertisement Loading ...