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Escherichia coli P fimbriae utilize the Toll-like receptor 4 pathway for cell activation

Frendeus, Björn; Wachtler, Caroline LU ; Hedlund, Maria; Fischer, Hans LU ; Samuelsson, Patrik LU ; Svensson, Majlis LU and Svanborg, Catharina LU (2001) In Molecular Microbiology 40(1). p.37-51
Abstract
Fimbriae mediate bacterial attachment to host cells and provide a mechanism for tissue attack. They activate a host response by delivery of microbial products such as lipopolysaccharide (LPS) or through direct fimbriae-dependent signalling mechanisms. By coupling to glycosphingolipid (GSL) receptors, P fimbriae trigger cytokine responses in CD14 negative host cells. Here we show that P fimbriae utilize the Toll-like receptor 4 (TLR4)-dependent pathway to trigger mucosal inflammation. Escherichia coli strains expressing P fimbriae as their only virulence factor stimulated chemokine and neutrophil responses in the urinary tract of TLR4 proficient mice, but TLR4 defective mice failed to respond to infection. Mucosal cells were CD14 negative... (More)
Fimbriae mediate bacterial attachment to host cells and provide a mechanism for tissue attack. They activate a host response by delivery of microbial products such as lipopolysaccharide (LPS) or through direct fimbriae-dependent signalling mechanisms. By coupling to glycosphingolipid (GSL) receptors, P fimbriae trigger cytokine responses in CD14 negative host cells. Here we show that P fimbriae utilize the Toll-like receptor 4 (TLR4)-dependent pathway to trigger mucosal inflammation. Escherichia coli strains expressing P fimbriae as their only virulence factor stimulated chemokine and neutrophil responses in the urinary tract of TLR4 proficient mice, but TLR4 defective mice failed to respond to infection. Mucosal cells were CD14 negative but expressed several TLR species including TLR4, and TLR4 protein was detected. Infection with P fimbriated bacteria stimulated an increase in TLR4 mRNA levels. The activation signal did not involve the LPS-CD14 pathway and was independent of lipid A myristoylation, as shown by mutational inactivation of the msbB gene. Co-staining experiments revealed that TLR4 and the GSL receptors for P fimbriae co-localized in the cell membrane. The results demonstrate that P fimbriae activate epithelial cells by means of a TLR4-dependent signalling pathway, and suggest that GSL receptors for P fimbriae can recruit TLR4 as co-receptors. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Molecular Microbiology
volume
40
issue
1
pages
37 - 51
publisher
Wiley-Blackwell
external identifiers
  • pmid:11298274
  • scopus:0035044165
ISSN
1365-2958
DOI
10.1046/j.1365-2958.2001.02361.x
language
English
LU publication?
yes
id
9619abf9-0a14-461e-ba6f-0ed8be3a5dd9 (old id 1121097)
date added to LUP
2008-06-27 13:17:58
date last changed
2018-05-29 11:31:11
@article{9619abf9-0a14-461e-ba6f-0ed8be3a5dd9,
  abstract     = {Fimbriae mediate bacterial attachment to host cells and provide a mechanism for tissue attack. They activate a host response by delivery of microbial products such as lipopolysaccharide (LPS) or through direct fimbriae-dependent signalling mechanisms. By coupling to glycosphingolipid (GSL) receptors, P fimbriae trigger cytokine responses in CD14 negative host cells. Here we show that P fimbriae utilize the Toll-like receptor 4 (TLR4)-dependent pathway to trigger mucosal inflammation. Escherichia coli strains expressing P fimbriae as their only virulence factor stimulated chemokine and neutrophil responses in the urinary tract of TLR4 proficient mice, but TLR4 defective mice failed to respond to infection. Mucosal cells were CD14 negative but expressed several TLR species including TLR4, and TLR4 protein was detected. Infection with P fimbriated bacteria stimulated an increase in TLR4 mRNA levels. The activation signal did not involve the LPS-CD14 pathway and was independent of lipid A myristoylation, as shown by mutational inactivation of the msbB gene. Co-staining experiments revealed that TLR4 and the GSL receptors for P fimbriae co-localized in the cell membrane. The results demonstrate that P fimbriae activate epithelial cells by means of a TLR4-dependent signalling pathway, and suggest that GSL receptors for P fimbriae can recruit TLR4 as co-receptors.},
  author       = {Frendeus, Björn and Wachtler, Caroline and Hedlund, Maria and Fischer, Hans and Samuelsson, Patrik and Svensson, Majlis and Svanborg, Catharina},
  issn         = {1365-2958},
  language     = {eng},
  number       = {1},
  pages        = {37--51},
  publisher    = {Wiley-Blackwell},
  series       = {Molecular Microbiology},
  title        = {Escherichia coli P fimbriae utilize the Toll-like receptor 4 pathway for cell activation},
  url          = {http://dx.doi.org/10.1046/j.1365-2958.2001.02361.x},
  volume       = {40},
  year         = {2001},
}