CXC Chemokine Receptor 2 Contributes to Host Defense in Murine Urinary Tract Infection

Olszyna, Dariusz P.; Florquin, Sandrine; Sewnath, Miguel E.; Branger, Judith; Speelman, Peter; Deventer, S. J. H. Van; Strieter, Robert M.; Poll, Tom van der

doi:10.1086/322030

Cited by 54 publications

(57 citation statements)

References 35 publications

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“…Altogether it seems that the role of CD44 in neutrophil adhesion, extravasation, and migration is at variance depending on the site of inflammation and the type of inflammatory diseases. Release of proinflammatory cytokines and chemokines by urothelial cells plays a beneficial role in the rapid induction of an appropriate inflammatory response to remove invading microorganisms during UTI (3,45,56). One of the mechanisms implicated in the activation of urothelial cells and their secretion of cytokines/ chemokines is the interaction between CD44 and HA that transforms CD44-positive TECs into an inflammatory phenotype characterized by the secretion of MCP-1, RANTES, and TNF-␣ (9).…”

Section: Discussionmentioning

confidence: 99%

“…For instillation of the bacteria we used a radiopaque catheter with a diameter of 0.55 mm (Abbott Laboratories). In these experiments, E. coli 1677 was used, which was isolated from a patient with UTI and was previously proven to be uropathogenic in mice during experimental pyelonephritis (43)(44)(45). At 6, 24, and 48 h after infection, mice (n ϭ 8 per group) were anesthetized by fentanyl, fluanisone, and midazolam mixture and were killed by cardiac exsanguination.…”

Section: Mice and Experimental Protocolmentioning

confidence: 99%

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Urothelial CD44 Facilitates Escherichia coli Infection of the Murine Urinary Tract

Rouschop¹,

Sylva²,

Teske³

et al. 2006

The Journal of Immunology

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Escherichia coli is the most common pathogen found in urinary tract infections (UTIs), mainly affecting children and women. We report that CD44, a hyaluronic acid (HA) binding protein that mediates cell-cell and cell-matrix interactions, facilitates the interaction of E. coli with urothelial cells and thus the infection of the host. We found that CD44 is constitutively expressed on urothelial cells and that HA accumulates in E. coli-induced UTI. In CD44-deficient mice, the bacterial outgrowth was dramatically less compared with wild-type mice despite similar granulocyte influx in the bladder and in the kidney as well as comparable cytokines/chemokines levels in both genotypes. E. coli was able to bind HA, which adhered to CD44-positive tubular epithelial cells. Most importantly, the interaction of CD44 on tubular epithelial cells with HA facilitated the migration of E. coli through the epithelial monolayer. The results provide evidence that CD44 on urothelial cells facilitates E. coli UTI. Disruption of the interaction between CD44 and HA in the bladder may provide a new approach to prevent and to treat UTI.

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Section: Discussionmentioning

confidence: 99%

Section: Mice and Experimental Protocolmentioning

confidence: 99%

Urothelial CD44 Facilitates Escherichia coli Infection of the Murine Urinary Tract

Rouschop¹,

Sylva²,

Teske³

et al. 2006

The Journal of Immunology

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“…The role of CXCR2 in neutrophil recruitment has been consistently reported (5)(6)(7)(8)(9)(10)(11)(12), but the role of CCR1 remains controversial. Although CCR1 or MIP-1␣ deficiency has been shown to inhibit neutrophil migration in some models (13,14,16), a lack of effect has been reported in other studies (7,44).…”

Section: Discussionmentioning

confidence: 99%

Resident Cell Chemokine Expression Serves as the Major Mechanism for Leukocyte Recruitment During Local Inflammation

García-Ramallo

Marques

Prats

et al. 2002

The Journal of Immunology

165

149

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The mechanistic relationships between initiating stimulus, cellular source and sequence of chemokine expression, and leukocyte recruitment during inflammation are not clear. To study these relationships in an acute inflammatory process, we challenged a murine air pouch with carrageenan. A time-dependent increase in TNF-␣, monocyte chemottractant protein-1 (MCP-1), macrophage-inflammatory protein-1␣ (MIP-1␣), RANTES, KC, and MIP-2 was found in the exudates preceding cell recruitment, but displaying different kinetic profiles. Air pouches generated for 2, 6, or 9 days before initiating inflammation demonstrated a proportional increase in the number of cells lining the cavities. Two hours after carrageenan stimulation, the synthesis of TNF-␣ and all chemokines but RANTES increased in proportion to the lining cellularity, although no differences in infiltrating leukocytes were found, suggesting that the early source of these mediators is resident cells. To assess the contribution of neutrophils to chemokine synthesis at later time points, we used neutropenic animals. Neutrophil depletion caused a decrease in TNF-␣ (51%), KC (37%), MIP-1␣ (30%), and RANTES (57%) levels and a 2-fold increase in monocytes 4 h after challenge. No effect on MIP-2 and MCP-1 levels was observed. The selective blockade of CXCR2 or CCR1 inhibited neutrophil recruitment by 74% and 54%, respectively, without a significant inhibition of monocytes. A differential effect on TNF-␣ and MCP-1 levels was observed after these treatments, indicating that the two receptors did not subserve a mere redundant chemotactic role. Overall, our results suggest that chemokines synthesized by resident cells play an important role in the evolution of the inflammatory response.

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“…Pyelonephritis (upper UTI) was induced as described before (7,24). Under general anesthesia (0.07 ml/10 g of body weight of FFM mixture, containing 1.25 mg/ml midazolam [Roche], 0.08 mg/ml fentanyl citrate, and 2.5 mg/ml fluanisone [Janssen Pharmaceutica]) TIR8 ϩ/ϩ and TIR8 Ϫ/Ϫ mice (n ϭ 7 to 11 per group) were administered via the urethra 5 ϫ 10 8 CFU per mouse in a volume of 100 l, as assessed by plating 10-fold serial dilutions of the suspension on blood agar plates.…”

Section: Methodsmentioning

confidence: 99%

“…Administering this volume did not lead to vesicoureteral reflux of bacteria, as determined by plating kidney homogenate of 3 animals 10 min after bacterial injection. Animals were sacrificed 4,8,24, and 48 h after inoculation. Sham control mice underwent the same procedure with administration of sterile PBS instead of bacterial suspension.…”

Section: Methodsmentioning

confidence: 99%

The Toll Interleukin-1 Receptor (IL-1R) 8/Single Ig Domain IL-1R-Related Molecule Modulates the Renal Response to Bacterial Infection

et al. 2012

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Our immune system has to constantly strike a balance between activation and inhibition of an inflammatory response to combat invading pathogens and avoid inflammation-induced collateral tissue damage. Toll interleukin-1 receptor 8 (IL-1R-8)/single Ig domain IL-1R-related molecule (TIR8/SIGIRR) is an inhibitor of Toll-like receptor (TLR)/IL-1R signaling, which is predominantly expressed in the kidney. The biological role of renal TIR8 during infection is, however, unknown. We therefore evaluated renal TIR8 expression during Escherichia coli pyelonephritis and explored its role in host defense using TIR8 ؊/؊ versus TIR8 ؉/؉ mice. We found that TIR8 protein is abundantly present in the majority of cortical tubular epithelial cells. Pyelonephritis resulted in a significant downregulation of TIR8 mRNA in kidneys of TIR8 ؉/؉ mice. TIR8 inhibited an effective host response against E. coli, as indicated by diminished renal bacterial outgrowth and dysfunction in TIR8 ؊/؊ mice. This correlated with increased amounts of circulating and intrarenal neutrophils at the early phase of infection. TIR8؊/؊ tubular epithelial cells had increased cytokine/chemokine production when stimulated with lipopolysaccharide (LPS) or heat-killed E. coli, suggesting that TIR8 played an anti-inflammatory role during pathogen stimulation by inhibiting LPS signaling. These data suggest that TIR8 is an important negative regulator of an LPS-mediated inflammatory response in tubular epithelial cells and dampens an effective antibacterial host response during pyelonephritis caused by uropathogenic E. coli.

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CXC Chemokine Receptor 2 Contributes to Host Defense in Murine Urinary Tract Infection

Cited by 54 publications

References 35 publications

Urothelial CD44 Facilitates Escherichia coli Infection of the Murine Urinary Tract

Urothelial CD44 Facilitates Escherichia coli Infection of the Murine Urinary Tract

Resident Cell Chemokine Expression Serves as the Major Mechanism for Leukocyte Recruitment During Local Inflammation

The Toll Interleukin-1 Receptor (IL-1R) 8/Single Ig Domain IL-1R-Related Molecule Modulates the Renal Response to Bacterial Infection

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