Format

Send to

Choose Destination

See 1 citation found by title matching your search:

Cell Microbiol. 2016 Nov;18(11):1570-1582. doi: 10.1111/cmi.12597. Epub 2016 May 3.

Moraxella catarrhalis induces CEACAM3-Syk-CARD9-dependent activation of human granulocytes.

Author information

1
Septomics Research Center, Jena University Hospital, Jena, Germany.
2
Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany.
3
Biofilmcenter, German Heart Institute Berlin, Berlin, Germany.
4
Department of Infectious Diseases and Pulmonary Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany.
5
Institute for Microbiology and Hygiene, Charité - Universitätsmedizin Berlin, Berlin, Germany.
6
Institute of Molecular and Clinical Immunology, Medical Faculty, Otto-von-Guericke University, Magdeburg, Germany.
7
Clinical Microbiology, Department of Translational Medicine, Lund University, Malmö, Sweden.
8
Institute of Anatomy, University Hospital, University Duisburg-Essen, Essen, Germany.
9
Institute of Vegetative Anatomy, Charité - Universitätsmedizin Berlin, Berlin, Germany.
10
Septomics Research Center, Jena University Hospital, Jena, Germany. hortense.slevogt@med.uni-jena.de.

Abstract

The human restricted pathogen Moraxella catarrhalis is an important causal agent for exacerbations in chronic obstructive lung disease in adults. In such patients, increased numbers of granulocytes are present in the airways, which correlate with bacteria-induced exacerbations and severity of the disease. Our study investigated whether the interaction of M. catarrhalis with the human granulocyte-specific carcinoembryonic antigen-related cell adhesion molecule (CEACAM)-3 is linked to NF-κB activation, resulting in chemokine production. Granulocytes from healthy donors and NB4 cells were infected with M. catarrhalis in the presence of different inhibitors, blocking antibodies and siRNA. The supernatants were analysed by enzyme-linked immunosorbent assay for chemokines. NF-κB activation was determined using a luciferase reporter gene assay and chromatin-immunoprecipitation. We found evidence that the specific engagement of CEACAM3 by M. catarrhalis ubiquitous surface protein A1 (UspA1) results in the activation of pro-inflammatory events, such as degranulation of neutrophils, ROS production and chemokine secretion. The interaction of UspA1 with CEACAM3 induced the activation of the NF-κB pathway via Syk and the CARD9 pathway and was dependent on the phosphorylation of the CEACAM3 ITAM-like motif. These findings suggest that the CEACAM3 signalling in neutrophils is able to specifically modulate airway inflammation caused by infection with M. catarrhalis.

KEYWORDS:

CARD9; CEACAM3; COPD; Moraxella catarrhalis; Syk; granulocyte; immunoreceptor tyrosine-based activation motif (ITAM)

PMID:
27038042
PMCID:
PMC5096018
DOI:
10.1111/cmi.12597
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center