Advanced

TLR- and CXCR1-dependent innate immunity: insights into the genetics of urinary tract infections.

Ragnarsdottir, Bryndis LU ; Fischer, Hans LU ; Godaly, Gabriela LU ; Grönberg Hernandez, Jenny LU ; Gustafsson, Mattias LU ; Karpman, Diana LU ; Lundstedt, Ann-Charlotte LU ; Lutay, Nataliya LU ; Rämisch, S and Svensson, M L, et al. (2008) In European Journal of Clinical Investigation 38 Suppl 2. p.12-20
Abstract
The susceptibility to urinary tract infection (UTI) is controlled by the innate immune response and Toll like receptors (TLRs) are the sentinels of this response. If productive, TLR4 signalling may initiate the symptomatic disease process. In the absence of TLR4 signalling the infected host instead develops an asymptomatic carrier state. The activation of mucosal TLR4 is also influenced by the properties of the infecting strain, and pathogens use their virulence factors to trigger 'pathogen-specific' TLR4 responses in the urinary tract but do not respond to the asymptomatic carrier strains in patients with asymptomatic bacteriuria (ABU). The TLR4 dependence has been demonstrated in mice and the relevance of low TLR4 function for protection... (More)
The susceptibility to urinary tract infection (UTI) is controlled by the innate immune response and Toll like receptors (TLRs) are the sentinels of this response. If productive, TLR4 signalling may initiate the symptomatic disease process. In the absence of TLR4 signalling the infected host instead develops an asymptomatic carrier state. The activation of mucosal TLR4 is also influenced by the properties of the infecting strain, and pathogens use their virulence factors to trigger 'pathogen-specific' TLR4 responses in the urinary tract but do not respond to the asymptomatic carrier strains in patients with asymptomatic bacteriuria (ABU). The TLR4 dependence has been demonstrated in mice and the relevance of low TLR4 function for protection for human disease was recently confirmed in children with asymptomatic bacteriuria, who expressed less TLR4 than age matched controls. Functional chemokines and functional chemokine receptors are crucial for neutrophil recruitment, and for the neutrophil dependent bacterial clearance. Interleukin (IL)-8 receptor deficient mice develop acute septic infections and chronic tissue damage, due to aberrant neutrophil function. This mechanism is relevant for human UTI as pyelonephritis prone children express low levels of the human CXCL8 (Il-8) receptor, CXC chemokine receptor 1 (CXCR1) and often have heterozygous CXCR1 polymorphisms. This review illustrates how intimately the innate response and the susceptibility to UTI are linked and sophisticated recognition mechanisms that rely on microbial virulence and on host TLR4 and CXCR1 signalling. (Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
European Journal of Clinical Investigation
volume
38 Suppl 2
pages
12 - 20
publisher
Wiley-Blackwell
external identifiers
  • wos:000262756500003
  • pmid:18826477
  • scopus:52649116492
ISSN
0014-2972
DOI
10.1111/j.1365-2362.2008.02004.x
language
English
LU publication?
yes
id
431ca8bd-3f62-413f-95c2-e667b4492626 (old id 1262673)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18826477?dopt=Abstract
date added to LUP
2008-11-06 15:45:40
date last changed
2017-02-22 11:44:36
@article{431ca8bd-3f62-413f-95c2-e667b4492626,
  abstract     = {The susceptibility to urinary tract infection (UTI) is controlled by the innate immune response and Toll like receptors (TLRs) are the sentinels of this response. If productive, TLR4 signalling may initiate the symptomatic disease process. In the absence of TLR4 signalling the infected host instead develops an asymptomatic carrier state. The activation of mucosal TLR4 is also influenced by the properties of the infecting strain, and pathogens use their virulence factors to trigger 'pathogen-specific' TLR4 responses in the urinary tract but do not respond to the asymptomatic carrier strains in patients with asymptomatic bacteriuria (ABU). The TLR4 dependence has been demonstrated in mice and the relevance of low TLR4 function for protection for human disease was recently confirmed in children with asymptomatic bacteriuria, who expressed less TLR4 than age matched controls. Functional chemokines and functional chemokine receptors are crucial for neutrophil recruitment, and for the neutrophil dependent bacterial clearance. Interleukin (IL)-8 receptor deficient mice develop acute septic infections and chronic tissue damage, due to aberrant neutrophil function. This mechanism is relevant for human UTI as pyelonephritis prone children express low levels of the human CXCL8 (Il-8) receptor, CXC chemokine receptor 1 (CXCR1) and often have heterozygous CXCR1 polymorphisms. This review illustrates how intimately the innate response and the susceptibility to UTI are linked and sophisticated recognition mechanisms that rely on microbial virulence and on host TLR4 and CXCR1 signalling.},
  author       = {Ragnarsdottir, Bryndis and Fischer, Hans and Godaly, Gabriela and Grönberg Hernandez, Jenny and Gustafsson, Mattias and Karpman, Diana and Lundstedt, Ann-Charlotte and Lutay, Nataliya and Rämisch, S and Svensson, M L and Wullt, Björn and Yadav, Manisha and Svanborg, Catharina},
  issn         = {0014-2972},
  language     = {eng},
  pages        = {12--20},
  publisher    = {Wiley-Blackwell},
  series       = {European Journal of Clinical Investigation},
  title        = {TLR- and CXCR1-dependent innate immunity: insights into the genetics of urinary tract infections.},
  url          = {http://dx.doi.org/10.1111/j.1365-2362.2008.02004.x},
  volume       = {38 Suppl 2},
  year         = {2008},
}