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Type 1 fimbriae deliver an LPS- and TLR4-dependent activation signal to CD14-negative cells

Hedlund, Maria; Frendeus, Björn; Wachtler, Caroline LU ; Hang, Long; Fischer, Hans LU and Svanborg, Catharina LU (2001) In Molecular Microbiology 39(3). p.542-552
Abstract
Fimbriae target bacteria to different mucosal surfaces and enhance the inflammatory response at these sites. Inflammation may be triggered by the fimbriae themselves or by fimbriae-dependent delivery of other host activating molecules such as lipopolysaccharide (LPS). Although LPS activates systemic inflammation through the CD14 and Toll-like receptor 4 (TLR4) pathways, mechanisms of epithelial cell activation by LPS are not well understood. These cells lack CD14 receptors and are unresponsive to pure LPS, but fimbriated Escherichia coli overcome this refractoriness and trigger epithelial cytokine responses. We now show that type 1 fimbriae can present an LPS- and TLR4-dependent signal to the CD14-negative epithelial cells. Human... (More)
Fimbriae target bacteria to different mucosal surfaces and enhance the inflammatory response at these sites. Inflammation may be triggered by the fimbriae themselves or by fimbriae-dependent delivery of other host activating molecules such as lipopolysaccharide (LPS). Although LPS activates systemic inflammation through the CD14 and Toll-like receptor 4 (TLR4) pathways, mechanisms of epithelial cell activation by LPS are not well understood. These cells lack CD14 receptors and are unresponsive to pure LPS, but fimbriated Escherichia coli overcome this refractoriness and trigger epithelial cytokine responses. We now show that type 1 fimbriae can present an LPS- and TLR4-dependent signal to the CD14-negative epithelial cells. Human uroepithelial cells were shown to express TLR4, and type 1 fimbriated E. coli strains triggered an LPS-dependent response in those cells. A similar LPS- and fimbriae-dependent response was observed in the urinary tract of TLR4-proficient mice, but not in TLR4-defective mice. The moderate inflammatory response in the TLR4-defective mice was fimbriae dependent but LPS independent. The results demonstrate that type 1 fimbriae present LPS to CD14-negative cells and that the TLR4 genotype determines this response despite the absence of CD14 on the target cells. The results illustrate how the host "sees" LPS and other microbial products not as purified molecules but as complexes, and that fimbriae determine the molecular context in which LPS is presented to host cells. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Molecular Microbiology
volume
39
issue
3
pages
542 - 552
publisher
Wiley-Blackwell
external identifiers
  • pmid:11169097
  • scopus:0035135138
ISSN
1365-2958
DOI
language
English
LU publication?
yes
id
5dca066d-9341-43eb-920f-fdb736f6c9cc (old id 1121115)
date added to LUP
2008-07-01 16:38:51
date last changed
2018-05-29 10:48:51
@article{5dca066d-9341-43eb-920f-fdb736f6c9cc,
  abstract     = {Fimbriae target bacteria to different mucosal surfaces and enhance the inflammatory response at these sites. Inflammation may be triggered by the fimbriae themselves or by fimbriae-dependent delivery of other host activating molecules such as lipopolysaccharide (LPS). Although LPS activates systemic inflammation through the CD14 and Toll-like receptor 4 (TLR4) pathways, mechanisms of epithelial cell activation by LPS are not well understood. These cells lack CD14 receptors and are unresponsive to pure LPS, but fimbriated Escherichia coli overcome this refractoriness and trigger epithelial cytokine responses. We now show that type 1 fimbriae can present an LPS- and TLR4-dependent signal to the CD14-negative epithelial cells. Human uroepithelial cells were shown to express TLR4, and type 1 fimbriated E. coli strains triggered an LPS-dependent response in those cells. A similar LPS- and fimbriae-dependent response was observed in the urinary tract of TLR4-proficient mice, but not in TLR4-defective mice. The moderate inflammatory response in the TLR4-defective mice was fimbriae dependent but LPS independent. The results demonstrate that type 1 fimbriae present LPS to CD14-negative cells and that the TLR4 genotype determines this response despite the absence of CD14 on the target cells. The results illustrate how the host "sees" LPS and other microbial products not as purified molecules but as complexes, and that fimbriae determine the molecular context in which LPS is presented to host cells.},
  author       = {Hedlund, Maria and Frendeus, Björn and Wachtler, Caroline and Hang, Long and Fischer, Hans and Svanborg, Catharina},
  issn         = {1365-2958},
  language     = {eng},
  number       = {3},
  pages        = {542--552},
  publisher    = {Wiley-Blackwell},
  series       = {Molecular Microbiology},
  title        = {Type 1 fimbriae deliver an LPS- and TLR4-dependent activation signal to CD14-negative cells},
  url          = {http://dx.doi.org/},
  volume       = {39},
  year         = {2001},
}