Uropathogenic E. coli promote a paracellular urothelial barrier defect characterized by altered tight junction integrity, epithelial cell sloughing and cytokine release.
The urinary bladder is a common site of bacterial infection with a majority of cases attributed to uropathogenic Escherichia coli. Sequelae of urinary tract infections (UTIs) include the loss of urothelial barrier function and subsequent clinical morbidity secondary to the permeation of urine potassium, urea and ammonia into the subepithelium. To date there has been limited research describing the mechanism by which this urothelial permeability defect develops. The present study models acute uropathogenic E. coli infection in vitro using intact canine bladder mucosa mounted in Ussing chambers to determine whether infection induces primarily a transcellular or paracellular permeability defect. The Ussing chamber sustains tissue viability while physically separating submucosal and lumen influences, so this model is ideal for quantitative measurement of transepithelial electrical resistance (TER) to assess alterations of urothelial barrier function. Using this model, changes in both tissue ultrastructure and TER indicated that uropathogenic E. coli infection promotes a paracellular permeability defect associated with the failure of umbrella cell tight junction formation and umbrella cell sloughing. In addition, bacterial interaction with the urothelium promoted secretion of cytokines from the urinary bladder with bioactivity capable of modulating epithelial barrier function including tumour necrosis factor-α, interleukin (IL)-6 and IL-15. IL-15 secretion by the infected bladder mucosa is a novel finding and, because IL-15 plays key roles in reconstitution of tight junction function in damaged intestine, this study points to a potential role for IL-15 in UTI-induced urothelial injury.
Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607, USA.
M W
MW
Wood
E B
EB
Breitschwerdt
S K
SK
Nordone
K E
KE
Linder
J L
JL
Gookin
D000818:Animals; D002463:Cell Membrane Permeability / Q000502:physiology; D016207:Cytokines / Q000378:metabolism*; D015194:Diffusion Chambers, Culture; D004285:Dogs; D004553:Electric Conductivity; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D019108:Tight Junctions / Q000473:pathology* / Q000648:ultrastructure; D046509:Tissue Culture Techniques; D001743:Urinary Bladder / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D056689:Uropathogenic Escherichia coli / Q000502:physiology*; D019459:Urothelium / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*
D016207:Cytokines