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PLoS One. 2014 Apr 17;9(4):e94106. doi: 10.1371/journal.pone.0094106. eCollection 2014.

Soluble CEACAM8 interacts with CEACAM1 inhibiting TLR2-triggered immune responses.

Author information

Institute of Anatomy, University Hospital, University Duisburg-Essen, Essen, Germany.
Institute of Microbiology and Hygiene, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
ZIK Septomics, University Hospital Jena, Jena, Germany.
Labor Berlin - Charité Vivantes Services GmbH, Berlin, Germany; Institute of Laboratory Medicine, Clinical Chemistry and Pathobiochemistry of the Charité Universitätsmedizin Berlin, Berlin, Germany.
Institute of Hygiene and Environmental Medicine, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.


Lower respiratory tract bacterial infections are characterized by neutrophilic inflammation in the airways. The carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 8 is expressed in and released by human granulocytes. Our study demonstrates that human granulocytes release CEACAM8 in response to bacterial DNA in a TLR9-dependent manner. Individuals with a high percentage of bronchial lavage fluid (BALF) granulocytes were more likely to have detectable levels of released CEACAM8 in the BALF than those with a normal granulocyte count. Soluble, recombinant CEACAM8-Fc binds to CEACAM1 expressed on human airway epithelium. Application of CEACAM8-Fc to CEACAM1-positive human pulmonary epithelial cells resulted in reduced TLR2-dependent inflammatory responses. These inhibitory effects were accompanied by tyrosine phosphorylation of the immunoreceptor tyrosine-based inhibitory motif (ITIM) of CEACAM1 and by recruitment of the phosphatase SHP-1, which could negatively regulate Toll-like receptor 2-dependent activation of the phosphatidylinositol 3-OH kinase-Akt kinase pathway. Our results suggest a new mechanism by which granulocytes reduce pro-inflammatory immune responses in human airways via secretion of CEACAM8 in neutrophil-driven bacterial infections.

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