Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The . gov means it’s official. Federal government websites often end in . gov or . mil VSports app下载. Before sharing sensitive information, make sure you’re on a federal government site. .

Https

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely. V体育官网.

. 2006 Nov;74(11):6100-7.
doi: 10.1128/IAI.00881-06. Epub 2006 Sep 11.

Tumor necrosis factor alpha- and inducible nitric oxide synthase-producing dendritic cells are rapidly recruited to the bladder in urinary tract infection but are dispensable for bacterial clearance

Daniel Engel  1 , Ulrich Dobrindt, André Tittel, Petra Peters, Juliane Maurer, Ines Gütgemann, Brigitte Kaissling, William Kuziel, Steffen Jung, Christian Kurts
Affiliations

Tumor necrosis factor alpha- and inducible nitric oxide synthase-producing dendritic cells are rapidly recruited to the bladder in urinary tract infection but are dispensable for bacterial clearance

Daniel Engel et al. Infect Immun. 2006 Nov.

"VSports最新版本" Abstract

The role of dendritic cells (DC) in urinary tract infections (UTI) is unknown. These cells contribute directly to the innate defense against various viral and bacterial infections. Here, we studied their role in UTI using an experimental model induced by transurethral instillation of the uropathogenic Escherichia coli (UPEC) strain 536 into C57BL/6 mice. While few DC were found in the uninfected bladder, many had been recruited after 24 h, mostly to the submucosa and uroepithelium. They expressed markers of activation and maturation and exhibited the CD11b+ F4/80+ CD8- Gr-1- myeloid subtype. Also, tumor necrosis factor alpha (TNF-alpha)- and inducible nitric oxide synthase (iNOS)-producing CD11bINT DC (Tip-DC) were detected, which recently were proposed to be critical in the defense against bacterial infections. However, Tip-DC-deficient CCR2-/- mice did not show reduced clearance of UPEC from the infected bladder VSports手机版. Moreover, clearance was also unimpaired in CD11c-DTR mice depleted of all DC by injection of diphtheria toxin. This may be explained by the abundance of granulocytes and of iNOS- and TNF-alpha-producing non-DC that were able to replace Tip-DC functionality. These findings demonstrate that some of the abundant DC recruited in UTI contributed innate immune effector functions, which were, however, dispensable in the microenvironment of the bladder. .

PubMed Disclaimer

Figures

FIG. 1.
FIG. 1.
Recruitment of DC in UTI to the bladder wall. C57BL/6 mice were injected transurethrally with 5 × 108 E. coli 536 cells. After 24 h, sections of the bladder were stained for CD11c and analyzed by immunohistochemistry (A and B), by immunofluorescence (C), or by electron microscopy (D and E). CD11c+ cells were brown (A and B) or red (C). Counterstaining was performed with methyl green (A and B) or Hoechst 33258 (C). The images are representative of more than 10 mice analyzed. The bars in the lower right corners indicate 20 μm (A to C), 4 μm (D), and 10 μm (E).
FIG. 2.
FIG. 2.
Kinetics of bacterial clearance and leukocyte infiltration in UTI. (A) C57BL/6 mice were injected transurethrally with 5 × 108 E. coli 536 cells. At various time points, bladders were rinsed extensively with PBS in situ and removed for analysis. To determine the bacterial load, the bladders were mechanically homogenized. Aliquots were dispersed on E. coli-Proteus-Streptococcus plates and incubated at 37°C. The CFU of UPEC strains were counted after 14 h. For the time point of infection, the number of instilled UPEC strains was given. (B) To determine the number of infiltrating leukocytes, bladders were digested with collagenase, filtered on 100-μm mesh, Fc receptors were blocked, and cells were stained for flow cytometrical analysis. The numbers of CD11c+ dendritic cells, F4/80+ CD11c− macrophages, and Gr1+ CD11c− F4/80− MHC-II− granulocytes were determined by adding standardized numbers of latex particles. Dead cells were excluded using Hoechst 33258. Separate mouse groups were used for determining bacterial and cell counts. Shown are the means ± standard deviations from one of three experiments with groups of five mice.
FIG. 3.
FIG. 3.
Characterization of vesical DC subpopulations in UTI. (A) C57BL/6 mice were infected with 5 × 108 E. coli 536 cells. After 24 h, vesical CD11c+ cells were isolated by collagenase digestion, Fc receptors were blocked, and expressions of the costimulatory molecules CD40, CD80, and CD86 and of MHC-II were determined. Expression profiles of noninfected (gray area) versus infected (transparent area with thick line) mice were overlaid in histograms. Numbers indicate the mean fluorescence intensities (MFI) of these two cell populations. (B) Viable CD11c+ cells from infected and noninfected mice were stained for the DC subtype markers CD11b, F4/80, Gr-1, and CD8α and analyzed by flow cytometry. Numbers indicate the cellular proportions in each quadrant. The area in the lower left dot plot indicates CD11bINT DC. Data are representative for >10 (A and B) individual experiments.
FIG. 4.
FIG. 4.
Tip-DC are recruited to the bladder in UTI. (A) C57BL/6 or CCR2−/− mice were injected transurethrally with 5 × 108 E. coli 536 cells. After 24 h, the bladders of infected mice and noninfected controls were digested with collagenase and stained for CD11c and for intracellular expression of iNOS and TNF-α without in vitro restimulation. (B and C) Vesical DC from infected mice were analyzed for CD11b (B) and CCR2 (C) expression. The thick line indicates expression by iNOS+/TNF-α+ CD11c+ Tip-DC, and the thin line indicates expression by iNOS−/TNF-α− CD11c+ DC. The gray area represents the isotype control. (D) C57BL/6 mice were infected with 5 × 108 E. coli 536.gfp cells. After 24 h, vesical DC were isolated and fluorescence uptake was determined on CD11bINT Tip-DC (thick line) and CD11bHI myeloid DC (thin line). The gray area shows background fluorescence after infection with nonfluorescent UPEC.
FIG. 5.
FIG. 5.
Neither CD11c+ nor other CCR2-dependent cells are required for clearance of UPEC in UTI. (A) CD11c-DTR mice, CCR2−/− mice, and C57BL/6 wild-type controls were injected transurethrally with 5 × 108 E. coli 536 cells. At various time points, the number of CFU per bladder was determined. Bladder weights did not significantly differ at 72 h after infection (wild type, 20.4 ± 1.8 mg; CCR2−/−, 21.2 ± 1.7 mg). (B) The numbers of CD11c+ DC (▪, •) and Gr1+ F4/80− MHC class II− granulocytes (□, ○) in DT-treated CD11c-DTR/GFP mice (▪, □) and in wild-type controls (•, ○) are given as means ± standard deviations from groups of five mice. Results are representative of four individual experiments.
FIG. 6.
FIG. 6.
CCR2-independent immune effector cells replace the functionality of Tip-DC in UTI. C57BL/6 or CCR2−/− mice were infected with 5 × 108 E. coli 536 cells. After 24 h, the bladders of infected mice and noninfected controls were digested with collagenase and stained for surface molecules. (A and B) The numbers of iNOS+ (A) and TNF-α+ (B) CD11c+ cells (gray bars) and those of iNOS+ (A) and TNF-α+ (B) CD11c− cells (white bars) in single-cell suspensions from the bladder were determined by flow cytometry. Bars were stacked to yield the total number of iNOS+ (A) or TNF-α+ (B) cells. (C and D) The numbers of granulocytes (C) and DC (D) in single-cell suspensions from the bladder were determined by flow cytometry. Shown are the means ± standard deviations from groups of five mice. Results are representative of three individual experiments.
See this image and copyright information in PMC

References

    1. Berger, H., J. Hacker, A. Juarez, C. Hughes, and W. Goebel. 1982. Cloning of the chromosomal determinants encoding hemolysin production and mannose-resistant hemagglutination in Escherichia coli. J. Bacteriol. 152:1241-1247. - PMC - PubMed
    1. Bouchelouche, K., L. Andresen, S. Alvarez, J. Nordling, O. H. Nielsen, and P. Bouchelouche. 2006. Interleukin-4 and 13 induce the expression and release of monocyte chemoattractant protein 1, interleukin-6 and stem cell factor from human detrusor smooth muscle cells: synergy with interleukin-1beta and tumor necrosis factor-alpha. J. Urol. 175:760-765. - PubMed
    1. Brzuszkiewicz, E., H. Brüggemann, H. Liesegang, M. Emmerth, T. Oelschlaeger, G. Nagy, K. Albermann, C. Wagner, C. Buchrieser, L. Emödy, G. Gottschalk, J. Hacker, and U. Dobrindt. 2006. How to become a uropathogen: comparative genomic analysis of extraintestinal pathogenic Escherichia coli strains. Proc. Natl. Acad. Sci. USA 103:12879-12884. - PMC - PubMed
    1. Chan, E. D., J. Chan, and N. W. Schluger. 2001. What is the role of nitric oxide in murine and human host defense against tuberculosis? Current knowledge. Am. J. Respir. Cell Mol. Biol. 25:606-612. - PubMed
    1. Chen, M. C., C. S. Mudge, and D. Klumpp. 2006. Urothelial lesion formation is mediated by TNFR1 during neurogenic cystitis. Am. J. Physiol. Renal Physiol. 291:F741-F749. - V体育ios版 - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources (V体育2025版)