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Acute pyelonephritis and renal scarring are caused by dysfunctional innate immunity in mCxcr2 heterozygous mice.

Svensson, Majlis LU ; Yadav, Manisha LU ; Holmqvist, Bo; Lutay, Nataliya LU ; Svanborg, Catharina LU and Godaly, Gabriela LU (2011) In Kidney International 80(10). p.1064-1072
Abstract
The CXCR1 receptor and chemokine CXCL8 (IL-8) support neutrophil-dependent clearance of uropathogenic Escherichia coli from the urinary tract. CXCR1 is reduced in children prone to pyelonephritis, and heterozygous hCXCR1 polymorphisms are more common in this patient group than in healthy individuals, strongly suggesting a disease association. Since murine CXCR2 (mCXCR2) is functionally similar to human CXCR1, we determined effects of gene heterozygosity on the susceptibility to urinary tract infection by infecting heterozygous (mCxcr2(+/-)) mice with uropathogenic Escherichia coli. Clearance of infection and tissue damage were assessed as a function of innate immunity in comparison to that in knockout (mCxcr2(-/-)) and wild-type... (More)
The CXCR1 receptor and chemokine CXCL8 (IL-8) support neutrophil-dependent clearance of uropathogenic Escherichia coli from the urinary tract. CXCR1 is reduced in children prone to pyelonephritis, and heterozygous hCXCR1 polymorphisms are more common in this patient group than in healthy individuals, strongly suggesting a disease association. Since murine CXCR2 (mCXCR2) is functionally similar to human CXCR1, we determined effects of gene heterozygosity on the susceptibility to urinary tract infection by infecting heterozygous (mCxcr2(+/-)) mice with uropathogenic Escherichia coli. Clearance of infection and tissue damage were assessed as a function of innate immunity in comparison to that in knockout (mCxcr2(-/-)) and wild-type (mCxcr2(+/+)) mice. Acute sepsis-associated mortality was increased and bacterial clearance drastically impaired in heterozygous compared to wild-type mice. Chemokine and neutrophil responses were delayed along with evidence of neutrophil retention and unresolved kidney inflammation 1 month after infection. This was accompanied by epithelial proliferation and subepithelial fibrosis. The heterozygous phenotype was intermediate, between knockout and wild-type mice, but specific immune cell infiltrates that accompany chronic infection in knockout mice were not found. Hence, the known heterozygous CXCR1 polymorphisms may predispose patients to acute pyelonephritis and urosepsis. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Kidney International
volume
80
issue
10
pages
1064 - 1072
publisher
Nature Publishing Group
external identifiers
  • wos:000296609800010
  • pmid:21814172
  • scopus:80255135573
ISSN
1523-1755
DOI
10.1038/ki.2011.257
language
English
LU publication?
yes
id
27a4c467-b2c0-41a6-bc11-a8251519d345 (old id 2151511)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21814172?dopt=Abstract
date added to LUP
2011-09-04 21:14:04
date last changed
2017-06-25 04:05:18
@article{27a4c467-b2c0-41a6-bc11-a8251519d345,
  abstract     = {The CXCR1 receptor and chemokine CXCL8 (IL-8) support neutrophil-dependent clearance of uropathogenic Escherichia coli from the urinary tract. CXCR1 is reduced in children prone to pyelonephritis, and heterozygous hCXCR1 polymorphisms are more common in this patient group than in healthy individuals, strongly suggesting a disease association. Since murine CXCR2 (mCXCR2) is functionally similar to human CXCR1, we determined effects of gene heterozygosity on the susceptibility to urinary tract infection by infecting heterozygous (mCxcr2(+/-)) mice with uropathogenic Escherichia coli. Clearance of infection and tissue damage were assessed as a function of innate immunity in comparison to that in knockout (mCxcr2(-/-)) and wild-type (mCxcr2(+/+)) mice. Acute sepsis-associated mortality was increased and bacterial clearance drastically impaired in heterozygous compared to wild-type mice. Chemokine and neutrophil responses were delayed along with evidence of neutrophil retention and unresolved kidney inflammation 1 month after infection. This was accompanied by epithelial proliferation and subepithelial fibrosis. The heterozygous phenotype was intermediate, between knockout and wild-type mice, but specific immune cell infiltrates that accompany chronic infection in knockout mice were not found. Hence, the known heterozygous CXCR1 polymorphisms may predispose patients to acute pyelonephritis and urosepsis.},
  author       = {Svensson, Majlis and Yadav, Manisha and Holmqvist, Bo and Lutay, Nataliya and Svanborg, Catharina and Godaly, Gabriela},
  issn         = {1523-1755},
  language     = {eng},
  number       = {10},
  pages        = {1064--1072},
  publisher    = {Nature Publishing Group},
  series       = {Kidney International},
  title        = {Acute pyelonephritis and renal scarring are caused by dysfunctional innate immunity in mCxcr2 heterozygous mice.},
  url          = {http://dx.doi.org/10.1038/ki.2011.257},
  volume       = {80},
  year         = {2011},
}