Ceramide as a TLR4 agonist; a putative signalling intermediate between sphingolipid receptors for microbial ligands and TLR4.
Fischer, Hans LU ; Ellström, Patrik ; Ekström-Holka, Kristina LU ; Gustafsson, Lotta LU
; Gustafsson, Mattias
LU
and Svanborg, Catharina
LU
(2007)
In Cellular Microbiology
9(5).
p.1239-1251
- Abstract
- Mucosal Toll-like receptors (TLRs) respond to pathogens, but remain inert to the indigenous flora, suggesting that the TLRs can receive pathogen-specific signals. For example, TLR4 signalling is activated in CD14-negative epithelial cells by P-fimbriated, uropathogenic Escherichia coli, but not by lipopolysaccharide. The fimbriae use glycosphingolipids as recognition receptors and there is release of ceramide, which is the membrane-anchoring domain of the receptors. In this study, ceramide was identified as a TLR4 agonist and as a putative signalling intermediate between the glycosphingolipid recognition receptors and TLR4. Exogenous ceramide activated a TLR4-dependent epithelial cell response, as shown by exposing stably transfected... (More)
- Mucosal Toll-like receptors (TLRs) respond to pathogens, but remain inert to the indigenous flora, suggesting that the TLRs can receive pathogen-specific signals. For example, TLR4 signalling is activated in CD14-negative epithelial cells by P-fimbriated, uropathogenic Escherichia coli, but not by lipopolysaccharide. The fimbriae use glycosphingolipids as recognition receptors and there is release of ceramide, which is the membrane-anchoring domain of the receptors. In this study, ceramide was identified as a TLR4 agonist and as a putative signalling intermediate between the glycosphingolipid recognition receptors and TLR4. Exogenous ceramide activated a TLR4-dependent epithelial cell response, as shown by exposing stably transfected TLR4-positive or -negative human embryonal kidney cells to C2 and C6 ceramide. A similar, TLR4-dependent response occurred after deliberate release of endogenous long-chained ceramide with sphingomyelinase. Microbial ligands with glycosphingolipid specificity (P fimbriae or the B subunit of Shiga toxin) were shown to increase the levels of ceramide and to trigger a TLR4-dependent response in epithelial cells. The results show that ceramide activates TLR4 signalling and suggest that this mechanism might allow pathogens to elicit mucosal TLR4 responses by perturbing sphingolipid receptors for virulence ligands like P fimbriae. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/164887
- author
- Fischer, Hans
LU
; Ellström, Patrik
; Ekström-Holka, Kristina
LU
; Gustafsson, Lotta
LU
; Gustafsson, Mattias
LU
and Svanborg, Catharina
LU
- organization
- publishing date
- 2007
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Cellular Microbiology
- volume
- 9
- issue
- 5
- pages
- 1239 - 1251
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- wos:000245506100014
- scopus:34047276820
- ISSN
- 1462-5814
- DOI
- 10.1111/j.1462-5822.2006.00867.x
- language
- English
- LU publication?
- yes
- id
- 4112b4e2-c416-460e-bac2-4f578227d453 (old id 164887)
- alternative location
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17223929&dopt=Abstract
- date added to LUP
- 2016-04-01 12:04:33
- date last changed
- 2025-01-15 05:25:53
@article{4112b4e2-c416-460e-bac2-4f578227d453,
abstract = {{Mucosal Toll-like receptors (TLRs) respond to pathogens, but remain inert to the indigenous flora, suggesting that the TLRs can receive pathogen-specific signals. For example, TLR4 signalling is activated in CD14-negative epithelial cells by P-fimbriated, uropathogenic Escherichia coli, but not by lipopolysaccharide. The fimbriae use glycosphingolipids as recognition receptors and there is release of ceramide, which is the membrane-anchoring domain of the receptors. In this study, ceramide was identified as a TLR4 agonist and as a putative signalling intermediate between the glycosphingolipid recognition receptors and TLR4. Exogenous ceramide activated a TLR4-dependent epithelial cell response, as shown by exposing stably transfected TLR4-positive or -negative human embryonal kidney cells to C2 and C6 ceramide. A similar, TLR4-dependent response occurred after deliberate release of endogenous long-chained ceramide with sphingomyelinase. Microbial ligands with glycosphingolipid specificity (P fimbriae or the B subunit of Shiga toxin) were shown to increase the levels of ceramide and to trigger a TLR4-dependent response in epithelial cells. The results show that ceramide activates TLR4 signalling and suggest that this mechanism might allow pathogens to elicit mucosal TLR4 responses by perturbing sphingolipid receptors for virulence ligands like P fimbriae.}},
author = {{Fischer, Hans and Ellström, Patrik and Ekström-Holka, Kristina and Gustafsson, Lotta and Gustafsson, Mattias and Svanborg, Catharina}},
issn = {{1462-5814}},
language = {{eng}},
number = {{5}},
pages = {{1239--1251}},
publisher = {{John Wiley & Sons Inc.}},
series = {{Cellular Microbiology}},
title = {{Ceramide as a TLR4 agonist; a putative signalling intermediate between sphingolipid receptors for microbial ligands and TLR4.}},
url = {{http://dx.doi.org/10.1111/j.1462-5822.2006.00867.x}},
doi = {{10.1111/j.1462-5822.2006.00867.x}},
volume = {{9}},
year = {{2007}},
}