Soluble CEACAM8 interacts with CEACAM1 inhibiting TLR2-triggered immune responses

Autor: Kerstin A. Heyl, Lena Opp, Bernhard B. Singer, Mario M. Müller, Luis Carlos Berrocal-Almanza, Janine Zweigner, Andreas Weimann, Annina Heinrich, Hortense Slevogt, Frauke Schreiber, Ramona Binding-Liermann
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Physiology
Medizin
lcsh:Medicine
Cell Count
Pathogenesis
Pathology and Laboratory Medicine
chemistry.chemical_compound
Cell Signaling
Animal Cells
Immune Physiology
Molecular Cell Biology
Medicine and Health Sciences
Membrane Receptor Signaling
Tyrosine
lcsh:Science
Multidisciplinary
Cell adhesion molecule
Immune Receptor Signaling
Cell biology
Chemistry
Host-Pathogen Interactions
Physical Sciences
Signal transduction
Cellular Types
Bronchoalveolar Lavage Fluid
Research Article
Signal Transduction
Protein Binding
Cytochalasin D
Immune Cells
Immunology
Bronchi
Biology
GPI-Linked Proteins
Microbiology
Cell Line
Immune system
Antigens
CD
Animals
Humans
Secretion
lcsh:R
Biology and Life Sciences
Tyrosine phosphorylation
Epithelial Cells
Cell Biology
Toll-Like Receptor 2
Toll-Like Receptor 9
Rats
TLR2
chemistry
Solubility
lcsh:Q
Clinical Immunology
Pulmonary Immunology
Cell Adhesion Molecules
Granulocytes
Zdroj: PLoS ONE
PLoS ONE, Vol 9, Iss 4, p e94106 (2014)
Popis: 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.
Databáze: OpenAIRE
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