scholarly journals A Newly Identified Role for IL-22 in Bladder Immunity

2020 ◽  
Author(s):  
Jared Honeycutt ◽  
Loc Le ◽  
Yi-Ju Hsieh ◽  
Michael H. Hsieh

AbstractBacterial and parasitic urinary tract infections(UTI) affect many, but our understanding of associated immunity remains poor. Prior work indicates interleukin-22(IL-22) is a key cytokine during infection of other epithelia. We hypothesized IL-22 is crucial during UTI.IL-22-null(KO) and wild-type(wt) mice underwent bladder wall injection with S. haematobium eggs or transurethral infection with uropathogenic E. coli UTI89.IL-22 and its soluble binding protein, IL-22BP, were increased in the bladder after S. haematobium egg injection. Genes typically induced by IL-22(CXCL2, REG3G[antimicrobial defense protein]], S100A8, S100A9, and Areg) were expressed at higher levels following S. haematobium egg injection. IL-22 stimulation of bladder tissue induced REG3B expression. IL-22 receptor alpha-1 expression was detectable in the urothelium by immunofluorescence and qPCR.Injection of S. haematobium eggs into IL-22-KO vs wt mice triggered differential expression of genes related to transferase activity(transferring alkyl or aryl groups) and epithelial cell development. Numerous uroplakin genes were downregulated in egg-injected, IL-22-KO mice versus their wt counterparts. These decreases in uroplakin expression suggest that, as in the gut, IL-22 is important for replenishing the epithelium during infection-related injury.Following transurethral infection with UTI89, IL-22-KO mice had lower bacterial counts in their urine, bladder, and kidneys. Giving stabilized IL-22 cytokine (IL-22-Fc) to UTI89-infected mice led to higher kidney bacterial counts and increased morbidity.Our data suggest that IL-22 is indeed important in urinary tract immunity, and may interfere with clearance of bacteria from the urinary tract, potentially through its role in maintenance of mature urothelium.

2013 ◽  
Vol 57 (11) ◽  
pp. 5197-5201 ◽  
Author(s):  
Katherine R. Ball ◽  
Francesca Sampieri ◽  
Manuel Chirino ◽  
Don L. Hamilton ◽  
Robert I. R. Blyth ◽  
...  

ABSTRACTA mouse model of cystitis caused by uropathogenicEscherichia coliwas used to study the distribution of gallium in bladder tissue following oral administration of gallium maltolate during urinary tract infection. The median concentration of gallium in homogenized bladder tissue from infected mice was 1.93 μg/g after daily administration of gallium maltolate for 5 days. Synchrotron X-ray fluorescence imaging and X-ray absorption spectroscopy of bladder sections confirmed that gallium arrived at the transitional epithelium, a potential site of uropathogenicE. coliinfection. Gallium and iron were similarly but not identically distributed in the tissues, suggesting that at least some distribution mechanisms are not common between the two elements. The results of this study indicate that gallium maltolate may be a suitable candidate for further development as a novel antimicrobial therapy for urinary tract infections caused by uropathogenicE. coli.


Antibiotics ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 170 ◽  
Author(s):  
Ashok Chockalingam ◽  
Sharron Stewart ◽  
Lin Xu ◽  
Adarsh Gandhi ◽  
Murali K. Matta ◽  
...  

Urinary tract infections (UTI) are common worldwide and are becoming increasingly difficult to treat because of the development of antibiotic resistance. Immunocompetent murine models of human UTI have been used to study pathogenesis and treatment but not for investigating resistance development after treatment with antibiotics. In this study, intravesical inoculation of uropathogenic Escherichia coli CFT073 in immunocompetent Balb/c mice was used as a model of human UTI. The value of the model in investigating antibiotic exposure on in vivo emergence of antibiotic resistance was examined. Experimentally infected mice were treated with 20 or 200 mg/kg ampicillin, 5 or 50 mg/kg ciprofloxacin, or 100 or 1000 mg/kg of fosfomycin. Ampicillin and ciprofloxacin were given twice daily at 8 h intervals, and fosfomycin was given once daily. Antibiotic treatment began 24 h after bacterial inoculation and ended after 72 h following the initial treatment. Although minimum inhibitory concentrations (MIC) for the experimental strain of E. coli were exceeded at peak concentrations in tissues and consistently in urine, low levels of bacteria persisted in tissues in all experiments. E. coli from bladder tissue, kidney, and urine grew on plates containing 1× MIC of antibiotic, but none grew at 3× MIC. This model is not suitable for studying emergent resistance but might serve to examine bacterial persistence.


2012 ◽  
Vol 57 (No. 7) ◽  
pp. 380-383 ◽  
Author(s):  
S. Kralova-Kovarikova ◽  
R. Husnik ◽  
D. Honzak ◽  
P. Kohout ◽  
P. Fictum

Stenotrophomonas maltophilia was isolated from three dogs with lower urinary tract disorders. The bacterium was cultured from bladder wall biopsy specimens obtained during cystoscopy, whereas urine culture was negative in all cases. The culture of biopsy specimens is useful and may help with the therapy even if diagnosis of the primary disease has been made.    


2007 ◽  
Vol 293 (5) ◽  
pp. F1736-F1745 ◽  
Author(s):  
Inga J. Murawski ◽  
David B. Myburgh ◽  
Jack Favor ◽  
Indra R. Gupta

Vesico-ureteric reflux (VUR) is a urinary tract abnormality that affects roughly one-third of patients with renal-coloboma syndrome, an autosomal dominant condition caused by a mutation in PAX2. Here, we report that a mouse model with an identical mutation, the Pax2 1Neu+/− mouse, has a 30% incidence of VUR. In VUR, urine flows retrogradely from the bladder to the ureter and is associated with urinary tract infections, hypertension, and renal failure. The propensity to reflux in the Pax2 1Neu+/− mouse is correlated with a shortened intravesical ureter that has lost its oblique angle of entry into the bladder wall compared with wild-type mice. Normally, the kidney and urinary tract develop from the ureteric bud, which grows from a predetermined position on the mesonephric duct. In Pax2 1Neu+/− mice, this position is shifted caudally while surrounding metanephric mesenchyme markers remain unaffected. Mutant offspring from crosses between Pax2 1Neu+/− and Hoxb7/GFP+/− mice have delayed union of the ureter with the bladder and delayed separation of the ureter from the mesonephric duct. These events are not caused by a change in apoptosis within the developing urinary tract. Our results provide the first evidence that VUR may arise from a delay in urinary tract maturation and an explanation for the clinical observation that VUR resolves over time in some affected children.


2004 ◽  
Vol 72 (12) ◽  
pp. 7294-7305 ◽  
Author(s):  
Angela M. Jansen ◽  
Virginia Lockatell ◽  
David E. Johnson ◽  
Harry L. T. Mobley

ABSTRACT Proteus mirabilis, an etiologic agent of complicated urinary tract infections, expresses mannose-resistant Proteus-like (MR/P) fimbriae whose expression is phase variable. Here we examine the role of these fimbriae in biofilm formation and colonization of the urinary tract. The majority of wild-type P. mirabilis cells in transurethrally infected mice produced MR/P fimbriae. Mutants that were phase-locked for either constitutive expression (MR/P ON) or the inability to express MR/P fimbriae (MR/P OFF) were phenotypically distinct and swarmed at different rates. The number of P. mirabilis cells adhering to bladder tissue did not appear to be affected by MR/P fimbriation. However, the pattern of adherence to the bladder surface was strikingly different. MR/P OFF colonized the lamina propria underlying exfoliated uroepithelium, while MR/P ON colonized the luminal surfaces of bladder umbrella cells and not the exfoliated regions. Wild-type P. mirabilis was usually found colonizing intact uroepithelium, but it occasionally adhered to exfoliated areas. MR/P ON formed significantly more biofilm than either P. mirabilis HI4320 (P = 0.03) or MR/P OFF (P = 0.05). MR/P OFF was able to form a biofilm similar to that of the wild type. MR/P ON formed a three-dimensional biofilm structure as early as 18 h after the initiation of the biofilm, while MR/P OFF and the wild type did not. After 7 days, however, P. mirabilis HI4320 formed a 65-μm-thick biofilm, while the thickest MR/P ON and MR/P OFF biofilms were only 12 μm thick. We concluded that MR/P fimbriae are expressed by most P. mirabilis cells infecting the urinary tract, dictate the localization of bacteria in the bladder, and contribute to biofilm formation.


2020 ◽  
Vol 185 (11-12) ◽  
pp. e2166-e2170
Author(s):  
Maeghan L Ciampa ◽  
James P Chohonis ◽  
Richard S Otto ◽  
Benjamin T Franklin

Abstract We report on a case of a healthy male patient who was referred to Urology for recurrent persistent urinary tract infections. Investigation revealed a large intraabdominal inflammatory collection abutting the cecum and bladder suspicious for ruptured appendicitis and colovesical fistula. He was taken to the operating room for exploratory laparotomy with General Surgery and Urology and found to have a ruptured appendix secondary to mucinous appendiceal neoplasm with invasion into the cecum and the bladder wall. He then underwent systemic chemotherapy followed by hyperthermic intraperitoneal chemotherapy. He is well with stable right lower quadrant inflammatory collection and without evidence of metastatic disease 22 months following initial surgery. This case presents a rare presentation of a rare disease process that is easy to misdiagnose or be delayed in diagnosis because of its vague and often varied presentation.


2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Ryan F. Peiffer ◽  
Carly Iulo ◽  
Tessa LeCuyer ◽  
Timothy Bolton

Abstract Background Corynebacterium urealyticum urinary tract infections can result in a rarely reported condition called encrusting cystitis whereby plaque lesions form on and within the urinary bladder mucosa. Chronic lower urinary tract signs manifest subsequent to the infection-induced cystitis and plaque-induced decreased bladder wall distensibility. Because of the organism’s multidrug resistance and plaque forming capability, infection eradication can be difficult. While systemic antimicrobial therapy is the mainstay of treatment, adjunctive surgical debridement of plaques has been used with relative paucity in such cases, thereby limiting our understanding of this modality’s indications and success rate. Consequently, this report describes the successful eradication of Corynebacterium urealyticum encrusting cystitis utilizing a unique timeline of medical and surgical treatments. Additionally, this represents the first reported veterinary case of a vasovagal reaction due to bladder overdistension. Case presentation A 6-year-old female spayed Miniature Schnauzer was evaluated for lower urinary tract clinical signs and diagnosed with Corynebacterium urealyticum encrusting cystitis. The infection was persistent despite prolonged courses of numerous oral antimicrobials and urinary acidification. A unique treatment timeline of intravenous vancomycin, intravesical gentamicin, and mid-course surgical debridement ultimately resulted in infection resolution. During surgery, while the urinary bladder was copiously flushed and distended with saline, the dog experienced an acute vasovagal reaction from which it fully recovered. Conclusions Surgical debridement of bladder wall plaques should be considered a viable adjunctive therapy for Corynebacterium urealyticum encrusting cystitis cases failing to respond to systemic antibiotic therapy. The timing in which surgery was employed in this case, relative to concurrent treatment modalities, may be applicable in future cases of this disease as dictated on a case-by-case basis. If surgery is ultimately pursued, overdistension of the urinary bladder should be avoided, or at least minimized as much as possible, so as to prevent the possibility of a vasovagal reaction.


2003 ◽  
Vol 47 (3) ◽  
pp. 1002-1009 ◽  
Author(s):  
M. B. Kerrn ◽  
N. Frimodt-Møller ◽  
F. Espersen

ABSTRACT Resistance to antibiotics used for the treatment of urinary tract infections (UTIs) is increasing worldwide. The impact of in vitro resistance on clinical outcome in UTIs requires further study, since most studies of both humans and animals have evaluated only the efficacy of antibiotics toward bacteria susceptible in vitro. We were interested in evaluating the relationship between the in vitro antibacterial effect and the in vivo efficacy after antibiotic treatment. We simulated a natural ascending UTI by use of the ascending UTI mouse model and used Escherichia coli strains with various susceptibilities to amdinocillin (mecillinam) and sulfamethizole. Mice were treated for 3 days with antibiotic doses approximating human urinary tract concentrations after a standard oral dose. For a susceptible strain (MIC, 0.5 μg/ml) and a resistant strain (MIC, 128 μg/ml), respectively, there were significant reductions in bacterial counts in the urine, bladder, and kidneys after treatment with amdinocillin, whereas for a strain for which the MIC was 16 μg/ml, there was a significant reduction in bacterial counts in the kidneys only (P < 0.05). Treatment with sulfamethizole resulted in a significant reduction in bacterial counts in all samples from a susceptible strain (MIC, 128 μg/ml) and a resistant strain (MIC, 512 μg/ml). Infection with a sulII gene-positive strain (MIC, >2,048 μg/ml) could not be treated with sulfamethizole, as no effect could be demonstrated in the urine, bladder, or kidneys. For amdinocillin, there was no clear-cut relationship between the in vitro susceptibility and the in vivo outcome, while for sulfamethizole, we found a relationship between the MIC for the strain and the effect in the urinary tract.


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