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CEACAM1 inhibits Toll-like receptor 2-triggered antibacterial responses of human pulmonary epithelial cells.
- Source :
-
Nature immunology [Nat Immunol] 2008 Nov; Vol. 9 (11), pp. 1270-8. Date of Electronic Publication: 2008 Oct 05. - Publication Year :
- 2008
-
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-kappaB-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.
- Subjects :
- Amino Acid Motifs physiology
Antigens, Bacterial immunology
Antigens, Bacterial metabolism
Antigens, CD chemistry
Bacterial Outer Membrane Proteins immunology
Bacterial Outer Membrane Proteins metabolism
Bronchi metabolism
Bronchi microbiology
Cell Adhesion Molecules chemistry
Cells, Cultured
Cytokines metabolism
Down-Regulation
Humans
NF-kappa B antagonists & inhibitors
NF-kappa B metabolism
Phosphatidylinositol 3-Kinases metabolism
Protein Tyrosine Phosphatase, Non-Receptor Type 6 metabolism
Proto-Oncogene Proteins c-akt metabolism
Respiratory Mucosa metabolism
Respiratory Mucosa microbiology
Signal Transduction immunology
Toll-Like Receptor 2 metabolism
Antigens, CD immunology
Bronchi immunology
Cell Adhesion Molecules immunology
Moraxella catarrhalis immunology
Neisseria meningitidis immunology
Respiratory Mucosa immunology
Toll-Like Receptor 2 immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1529-2916
- Volume :
- 9
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Nature immunology
- Publication Type :
- Academic Journal
- Accession number :
- 18836450
- Full Text :
- https://doi.org/10.1038/ni.1661