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Moraxella catarrhalis induces CEACAM3-Syk-Card9-dependent activation of human granulocytes

Heinrich, A; Heyl, K A; Klaile, E; Müller, M M; Klassert, T E; Wiessner, A; Fischer, K; Schumann, R R; Seifert, U and Riesbeck, K LU , et al. (2016) In Cellular Microbiology
Abstract

The human restricted pathogen Moraxella catarrhalis is an important causal agent for exacerbations in chronic obstructive lung disease (COPD) 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 ELISA for... (More)

The human restricted pathogen Moraxella catarrhalis is an important causal agent for exacerbations in chronic obstructive lung disease (COPD) 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 ELISA 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 Moraxella 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.

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Cellular Microbiology
publisher
Wiley-Blackwell
external identifiers
  • Scopus:84965117914
ISSN
1462-5814
DOI
10.1111/cmi.12597
language
English
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yes
id
3a5abf41-c16c-4a3b-9d6d-7cd4c10054ca
date added to LUP
2016-04-26 11:39:09
date last changed
2016-10-13 05:06:59
@misc{3a5abf41-c16c-4a3b-9d6d-7cd4c10054ca,
  abstract     = {<p>The human restricted pathogen Moraxella catarrhalis is an important causal agent for exacerbations in chronic obstructive lung disease (COPD) 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 ELISA 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 Moraxella 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.</p>},
  author       = {Heinrich, A and Heyl, K A and Klaile, E and Müller, M M and Klassert, T E and Wiessner, A and Fischer, K and Schumann, R R and Seifert, U and Riesbeck, K and Moter, A and Singer, B B and Bachmann, S and Slevogt, H},
  issn         = {1462-5814},
  language     = {eng},
  month        = {03},
  publisher    = {ARRAY(0x9294c38)},
  series       = {Cellular Microbiology},
  title        = {Moraxella catarrhalis induces CEACAM3-Syk-Card9-dependent activation of human granulocytes},
  url          = {http://dx.doi.org/10.1111/cmi.12597},
  year         = {2016},
}