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Subversion of Toll-like receptor signaling by a unique family of bacterial Toll/interleukin-1 receptor domain-containing proteins

Cirl, Christine; Wieser, Andreas; Yadav, Manisha LU ; Duerr, Susanne; Schubert, Sören; Fischer, Hans LU ; Stappert, Dominik; Wantia, Nina; Rodriguez, Nuria and Wagner, Hermann, et al. (2008) In Nature Medicine 14(4). p.399-406
Abstract
Pathogenic microbes have evolved sophisticated molecular strategies to subvert host defenses. Here we show that virulent bacteria interfere directly with Toll-like receptor (TLR) function by secreting inhibitory homologs of the Toll/interleukin-1 receptor (TIR) domain. Genes encoding TIR domain containing–proteins (Tcps) were identified in Escherichia coli CFT073 (TcpC) and Brucella melitensis (TcpB). We found that TcpC is common in the most virulent uropathogenic E. coli strains and promotes bacterial survival and kidney pathology in vivo. In silico analysis predicted significant tertiary structure homology to the TIR domain of human TLR1, and we show that the Tcps impede TLR signaling through the myeloid differentiation factor 88 (MyD88)... (More)
Pathogenic microbes have evolved sophisticated molecular strategies to subvert host defenses. Here we show that virulent bacteria interfere directly with Toll-like receptor (TLR) function by secreting inhibitory homologs of the Toll/interleukin-1 receptor (TIR) domain. Genes encoding TIR domain containing–proteins (Tcps) were identified in Escherichia coli CFT073 (TcpC) and Brucella melitensis (TcpB). We found that TcpC is common in the most virulent uropathogenic E. coli strains and promotes bacterial survival and kidney pathology in vivo. In silico analysis predicted significant tertiary structure homology to the TIR domain of human TLR1, and we show that the Tcps impede TLR signaling through the myeloid differentiation factor 88 (MyD88) adaptor protein, owing to direct binding of Tcps to MyD88. Tcps represent a new class of virulence factors that act by inhibiting TLR- and MyD88-specific signaling, thus suppressing innate immunity and increasing virulence. (Less)
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Contribution to journal
publication status
published
subject
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Nature Medicine
volume
14
issue
4
pages
399 - 406
publisher
Nature Publishing Group
external identifiers
  • wos:000254674100026
  • scopus:41849102701
ISSN
1546-170X
DOI
10.1038/nm1734
language
English
LU publication?
yes
id
0802a4bf-e3bd-4b5e-b340-f36ae478a8c8 (old id 1144683)
date added to LUP
2008-08-15 10:43:12
date last changed
2017-05-21 04:44:51
@article{0802a4bf-e3bd-4b5e-b340-f36ae478a8c8,
  abstract     = {Pathogenic microbes have evolved sophisticated molecular strategies to subvert host defenses. Here we show that virulent bacteria interfere directly with Toll-like receptor (TLR) function by secreting inhibitory homologs of the Toll/interleukin-1 receptor (TIR) domain. Genes encoding TIR domain containing–proteins (Tcps) were identified in Escherichia coli CFT073 (TcpC) and Brucella melitensis (TcpB). We found that TcpC is common in the most virulent uropathogenic E. coli strains and promotes bacterial survival and kidney pathology in vivo. In silico analysis predicted significant tertiary structure homology to the TIR domain of human TLR1, and we show that the Tcps impede TLR signaling through the myeloid differentiation factor 88 (MyD88) adaptor protein, owing to direct binding of Tcps to MyD88. Tcps represent a new class of virulence factors that act by inhibiting TLR- and MyD88-specific signaling, thus suppressing innate immunity and increasing virulence.},
  author       = {Cirl, Christine and Wieser, Andreas and Yadav, Manisha and Duerr, Susanne and Schubert, Sören and Fischer, Hans and Stappert, Dominik and Wantia, Nina and Rodriguez, Nuria and Wagner, Hermann and Svanborg, Catharina and Miethke, Thomas},
  issn         = {1546-170X},
  language     = {eng},
  number       = {4},
  pages        = {399--406},
  publisher    = {Nature Publishing Group},
  series       = {Nature Medicine},
  title        = {Subversion of Toll-like receptor signaling by a unique family of bacterial Toll/interleukin-1 receptor domain-containing proteins},
  url          = {http://dx.doi.org/10.1038/nm1734},
  volume       = {14},
  year         = {2008},
}