Early Severe Inflammatory Responses to Uropathogenic E. coli Predispose to Chronic and Recurrent Urinary Tract Infection (original) (raw)
Figure 1
C3H/HeN mice develop chronic cystitis in response to UPEC infection in an infectious dose-dependent manner.
A–B, Representative urine bacterial titer time course over 4 wpi with 107 cfu UTI89 KanR in A, C57BL/6J and B, C3H/HeN mice. Solid lines connect the urine titers over time for each individual mouse. Dashed horizontal line represents the cutoff for significant bacteriuria in free catch urines: 104 cfu/ml. C–D, Urine (U), bladder (B) and kidney (K) titers of C, C57BL/6J and D, C3H/HeN mice at 4 wpi with 107 or 108 cfu UTI89 KanR or UTI89, grouped by outcome: resolved bacteriuria (Resolved) or persistent bacteriuria (PB). Solid lines connect the different urine and tissue titers from the same mouse. Dotted horizontal lines show the limits of detection. E–H, Paraffin-embedded bladder sections 4 wpi with UTI89 KanR were examined by E–F, Hematoxylin & eosin (H&E) staining and light microscopy, or G–H, indirect immunofluorescence (IF) microscopy, staining with antibodies against E. coli (green) and uroplakin III (red); nuclei are counterstained with bis-benzimide (blue). Bladder sections from mice that resolved bacteriuria are displayed in panels E and G; from persistently bacteriuric mice in panels F and H. In panel H, arrows indicate luminal clusters of bacteria associated with immune and exfoliated urothelial cells. I–J, Frozen sections of the bladder of a persistently bacteriuric C3H/HeN mouse at 7.5 months post-infection with UTI89 were examined: I, H&E stained section of the trigone region (area of bladder near urethra where ureters enter), J, IF micrograph of a serial section of I, staining for CD45 (red) and the FimH adhesin of E. coli (green); nuclei are counterstained with bis-benzimide (blue). In panels E–J, bars approximate 50µm, “_L_” indicates bladder lumen, and dashed line denotes the approximate location of the urothelial basement membrane.