TLR- and CXCR1-dependent innate immunity: insights into the genetics of urinary tract infections.
(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:
https://lup.lub.lu.se/record/1262673
- author
- organization
- publishing date
- 2008
- 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
- pmid:18826477
- 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
- 2016-04-04 07:07:00
- date last changed
- 2023-09-19 10:55:14
@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}}, doi = {{10.1111/j.1365-2362.2008.02004.x}}, volume = {{38 Suppl 2}}, year = {{2008}}, }