CEACAM1 inhibits Toll-like receptor 2-triggered antibacterial responses of human pulmonary epithelial cells.
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.
Slevogt
Hortense
H
Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany. hortense.slevogt@charite.de
Zabel
Solveig
S
Opitz
Bastian
B
Hocke
Andreas
A
Eitel
Julia
J
N'guessan
Philippe D
PD
Lucka
Lothar
L
Riesbeck
Kristian
K
Zimmermann
Wolfgang
W
Zweigner
Janine
J
Temmesfeld-Wollbrueck
Bettina
B
Suttorp
Norbert
N
Singer
Bernhard B
BB
D020816:Amino Acid Motifs / Q000502:physiology; D000942:Antigens, Bacterial / Q000276:immunology / Q000378:metabolism; D015703:Antigens, CD / Q000737:chemistry / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology / Q000378:metabolism; D001980:Bronchi / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation; D006801:Humans; D001936:Moraxella catarrhalis / Q000276:immunology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009345:Neisseria meningitidis / Q000276:immunology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020545:Respiratory Mucosa / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D015398:Signal Transduction / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000276:immunology* / Q000378:metabolism
D000942:Antigens, Bacterial; D015703:Antigens, CD; D001425:Bacterial Outer Membrane Proteins; D015815:Cell Adhesion Molecules; D016207:Cytokines; D016328:NF-kappa B; D019869:Phosphatidylinositol 3-Kinases; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D051057:Proto-Oncogene Proteins c-akt; D051195:Toll-Like Receptor 2; C069847:CD66 antigens; C089675:UspA protein, Moraxella catarrhalis; C090348:Opa protein, Neisseria; C509249:PTPN6 protein, human