You have accessJournal of UrologyInfections/Inflammation of the Genitourinary Tract: Kidney & Bladder1 Apr 2012905 IL-33 SUPPRESSES PROTECTIVE IMMUNITY TO UROPATHOGENIC E. COLI BY STIMULATING B1 CELLS Vladimir Pavlov, Waltenbaugh Carl, Paul Bryce, Sara Conolly, Douglas Kuperman, Anthony Schaeffer, and David Klumpp Vladimir PavlovVladimir Pavlov Chicago, IL More articles by this author , Waltenbaugh CarlWaltenbaugh Carl Chicago, IL More articles by this author , Paul BrycePaul Bryce Chicago, IL More articles by this author , Sara ConollySara Conolly Chicago, IL More articles by this author , Douglas KupermanDouglas Kuperman Chicago, IL More articles by this author , Anthony SchaefferAnthony Schaeffer Chicago, IL More articles by this author , and David KlumppDavid Klumpp Chicago, IL More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.1001AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Th2–mediated humoral immunity protects against extracellular pathogens, but the role of Th2 cytokines in UTI is unknown. Here, we examine Th2 cytokines in response to bladder infection by uropathogenic E.coli (UPEC). We performed cytokine array for urinary bladder tissue as well as draining lymph nodes and found increased level of IL-13 and IL33. Therefore we have aimed to show the physiological role and significance of this cytokine in immunity against UPEC. METHODS C57BL/6 or STAT6-deficient or B cell-deficient mice were instilled via transurethral catheter with UPEC cystitis isolate NU14. Cytokines were quantified in urine and bladder homogenates by cytokine arrays and ELISA, and immunohistochemistry was used to localize expression. Flow cytometry was used to quantify leukocyte subsets and to identify cells secreting IL-33 and IL-13. Urinary IL-33 and IL-13 of UTI patients were analyzed by ELISA. RESULTS We observed that NU14 induced IL-33 cytokine production in a STAT6-dependent manner. IL-33 expression was produced in the urothelium and was dependent upon TLR2/4. IL-33 stimulated production of the Th2 effector cytokines IL-13 and IL-5 from the B1 subset of B cells. Either B cell deficiency or abrogation of IL-33 in STAT6-/- mice enhanced NU14 clearance, suggesting a counter-productive role for B1 cell production of Th2 cytokines. Consistent with this possibility, neutrophil influx in response to NU14 was enhanced in the absence of Th2 cytokines or B cells. Urine samples from patients with urinary tract infections revealed elevated levels of both IL-33 and IL-13, consistent with a similar role for Th2 cytokines in human UTI. CONCLUSIONS IL-33/IL-13 axis is activated during UPEC infection, thereby activating B1 cells, suppressing neutrophil influx, and impacting bacterial clearance. Thus, skewing Th2 cytokine responses is a therapeutic target for enhancing bacterial clearance and promoting effective bladder immunity. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e369 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Vladimir Pavlov Chicago, IL More articles by this author Waltenbaugh Carl Chicago, IL More articles by this author Paul Bryce Chicago, IL More articles by this author Sara Conolly Chicago, IL More articles by this author Douglas Kuperman Chicago, IL More articles by this author Anthony Schaeffer Chicago, IL More articles by this author David Klumpp Chicago, IL More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...