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Susceptibility to acute pyelonephritis or asymptomatic bacteriuria: Host-pathogen interaction in urinary tract infections.

Ragnarsdottir, Bryndis LU and Svanborg, Catharina LU (2012) In Pediatric Nephrology 27(11). p.2017-2029
Abstract
Our knowledge of the molecular mechanisms of urinary tract infection (UTI) pathogenesis has advanced greatly in recent years. In this review, we provide a general background of UTI pathogenesis, followed by an update on the mechanisms of UTI susceptibility, with a particular focus on genetic variation affecting innate immunity. The innate immune response of the host is critically important in the antibacterial defence mechanisms of the urinary tract, and bacterial clearance normally proceeds without sequelae. However, slight dysfunctions in these mechanisms may result in acute disease and tissue destruction. The symptoms of acute pyelonephritis are caused by the innate immune response, and inflammation in the urinary tract decreases renal... (More)
Our knowledge of the molecular mechanisms of urinary tract infection (UTI) pathogenesis has advanced greatly in recent years. In this review, we provide a general background of UTI pathogenesis, followed by an update on the mechanisms of UTI susceptibility, with a particular focus on genetic variation affecting innate immunity. The innate immune response of the host is critically important in the antibacterial defence mechanisms of the urinary tract, and bacterial clearance normally proceeds without sequelae. However, slight dysfunctions in these mechanisms may result in acute disease and tissue destruction. The symptoms of acute pyelonephritis are caused by the innate immune response, and inflammation in the urinary tract decreases renal tubular function and may give rise to renal scarring, especially in paediatric patients. In contrast, in children with asymptomatic bacteriuria (ABU), bacteria persist without causing symptoms or pathology. Pathogenic agents trigger a response determined by their virulence factors, mediating adherence to the urinary tract mucosa, signalling through Toll-like receptors (TLRs) and activating the defence mechanisms. In ABU strains, such virulence factors are mostly not expressed. However, the influence of the host on UTI severity cannot be overestimated, and rapid progress is being made in clarifying host susceptibility mechanisms. For example, genetic alterations that reduce TLR4 function are associated with ABU, while polymorphisms reducing IRF3 or CXCR1 expression are associated with acute pyelonephritis and an increased risk for renal scarring. It should be plausible to "individualize" diagnosis and therapy by combining information on bacterial virulence and the host response. (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
Pediatric Nephrology
volume
27
issue
11
pages
2017 - 2029
publisher
Springer
external identifiers
  • WOS:000309342000003
  • PMID:22327887
  • Scopus:84868119443
ISSN
1432-198X
DOI
10.1007/s00467-011-2089-1
language
English
LU publication?
yes
id
deeed91b-52be-4a8c-923b-19487fe02a66 (old id 2366992)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22327887?dopt=Abstract
date added to LUP
2012-03-02 11:12:55
date last changed
2016-11-13 04:27:00
@misc{deeed91b-52be-4a8c-923b-19487fe02a66,
  abstract     = {Our knowledge of the molecular mechanisms of urinary tract infection (UTI) pathogenesis has advanced greatly in recent years. In this review, we provide a general background of UTI pathogenesis, followed by an update on the mechanisms of UTI susceptibility, with a particular focus on genetic variation affecting innate immunity. The innate immune response of the host is critically important in the antibacterial defence mechanisms of the urinary tract, and bacterial clearance normally proceeds without sequelae. However, slight dysfunctions in these mechanisms may result in acute disease and tissue destruction. The symptoms of acute pyelonephritis are caused by the innate immune response, and inflammation in the urinary tract decreases renal tubular function and may give rise to renal scarring, especially in paediatric patients. In contrast, in children with asymptomatic bacteriuria (ABU), bacteria persist without causing symptoms or pathology. Pathogenic agents trigger a response determined by their virulence factors, mediating adherence to the urinary tract mucosa, signalling through Toll-like receptors (TLRs) and activating the defence mechanisms. In ABU strains, such virulence factors are mostly not expressed. However, the influence of the host on UTI severity cannot be overestimated, and rapid progress is being made in clarifying host susceptibility mechanisms. For example, genetic alterations that reduce TLR4 function are associated with ABU, while polymorphisms reducing IRF3 or CXCR1 expression are associated with acute pyelonephritis and an increased risk for renal scarring. It should be plausible to "individualize" diagnosis and therapy by combining information on bacterial virulence and the host response.},
  author       = {Ragnarsdottir, Bryndis and Svanborg, Catharina},
  issn         = {1432-198X},
  language     = {eng},
  number       = {11},
  pages        = {2017--2029},
  publisher    = {ARRAY(0x787d6e8)},
  series       = {Pediatric Nephrology},
  title        = {Susceptibility to acute pyelonephritis or asymptomatic bacteriuria: Host-pathogen interaction in urinary tract infections.},
  url          = {http://dx.doi.org/10.1007/s00467-011-2089-1},
  volume       = {27},
  year         = {2012},
}