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CEACAM1 inhibits Toll-like receptor 2-triggered antibacterial responses of human pulmonary epithelial cells

Slevogt, Hortense; Zabel, Solveig; Opitz, Bastian; Hocke, Andreas; Eitel, Julia; N'Guessan, Philippe D.; Lucka, Lothar; Riesbeck, Kristian LU ; Zimmermann, Wolfgang and Zweigner, Janine, et al. (2008) In Nature Immunology 9(11). p.1270-1278
Abstract
Although Moraxella catarrhalis and Neisseria meningitidis are important human pathogens, they often colonize the human respiratory tract without causing overt clinical symptoms. Both pathogens express structurally unrelated proteins that share the ability to stimulate the adhesion molecule CEACAM1 expressed on human cells. Here we demonstrate that the interaction of CEACAM1 with ubiquitous surface protein A1 expressed on M. catarrhalis or with opacity-associated proteins on N. meningitidis resulted in reduced Toll-like receptor 2-initiated transcription factor NF-kappa B-dependent inflammatory responses of primary pulmonary epithelial cells. These inhibitory effects were mediated by tyrosine phosphorylation of the immunoreceptor... (More)
Although Moraxella catarrhalis and Neisseria meningitidis are important human pathogens, they often colonize the human respiratory tract without causing overt clinical symptoms. Both pathogens express structurally unrelated proteins that share the ability to stimulate the adhesion molecule CEACAM1 expressed on human cells. Here we demonstrate that the interaction of CEACAM1 with ubiquitous surface protein A1 expressed on M. catarrhalis or with opacity-associated proteins on N. meningitidis resulted in reduced Toll-like receptor 2-initiated transcription factor NF-kappa B-dependent inflammatory responses of primary pulmonary epithelial cells. These inhibitory effects were mediated by tyrosine phosphorylation of the immunoreceptor tyrosine-based inhibitory motif of CEACAM1 and by recruitment of the phosphatase SHP-1, which negatively regulated Toll-like receptor 2-dependent activation of the phosphatidylinositol 3-OH kinase-Akt kinase pathway. Our results identify a CEACAM1-dependent immune-evasion strategy. (Less)
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publication status
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Nature Immunology
volume
9
issue
11
pages
1270 - 1278
publisher
Nature Publishing Group
external identifiers
  • wos:000260248600014
  • scopus:54549099000
ISSN
1529-2908
DOI
10.1038/ni.1661
language
English
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yes
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df764fd4-7bc9-43d9-8689-96e840f26acb (old id 1284596)
date added to LUP
2009-02-09 10:03:11
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2017-10-01 04:28:37
@article{df764fd4-7bc9-43d9-8689-96e840f26acb,
  abstract     = {Although Moraxella catarrhalis and Neisseria meningitidis are important human pathogens, they often colonize the human respiratory tract without causing overt clinical symptoms. Both pathogens express structurally unrelated proteins that share the ability to stimulate the adhesion molecule CEACAM1 expressed on human cells. Here we demonstrate that the interaction of CEACAM1 with ubiquitous surface protein A1 expressed on M. catarrhalis or with opacity-associated proteins on N. meningitidis resulted in reduced Toll-like receptor 2-initiated transcription factor NF-kappa B-dependent inflammatory responses of primary pulmonary epithelial cells. These inhibitory effects were mediated by tyrosine phosphorylation of the immunoreceptor tyrosine-based inhibitory motif of CEACAM1 and by recruitment of the phosphatase SHP-1, which negatively regulated Toll-like receptor 2-dependent activation of the phosphatidylinositol 3-OH kinase-Akt kinase pathway. Our results identify a CEACAM1-dependent immune-evasion strategy.},
  author       = {Slevogt, Hortense and Zabel, Solveig and Opitz, Bastian and Hocke, Andreas and Eitel, Julia and N'Guessan, Philippe D. and Lucka, Lothar and Riesbeck, Kristian and Zimmermann, Wolfgang and Zweigner, Janine and Temmesfeld-Wollbrueck, Bettina and Suttorp, Norbert and Singer, Bernhard B.},
  issn         = {1529-2908},
  language     = {eng},
  number       = {11},
  pages        = {1270--1278},
  publisher    = {Nature Publishing Group},
  series       = {Nature Immunology},
  title        = {CEACAM1 inhibits Toll-like receptor 2-triggered antibacterial responses of human pulmonary epithelial cells},
  url          = {http://dx.doi.org/10.1038/ni.1661},
  volume       = {9},
  year         = {2008},
}