Format

Send to

Choose Destination
Am J Physiol Lung Cell Mol Physiol. 2015 Aug 1;309(3):L250-61. doi: 10.1152/ajplung.00265.2014. Epub 2015 Jun 5.

Moraxella catarrhalis induces an immune response in the murine lung that is independent of human CEACAM5 expression and long-term smoke exposure.

Author information

1
Department of Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany;
2
Department of Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany; Septomics Research Center, Jena University Hospital, Jena, Germany;
3
Septomics Research Center, Jena University Hospital, Jena, Germany;
4
Department of Internal Medicine V-Pulmonology, Allergology, Respiratory Intensive Care Medicine, University of the Saarland, Homburg Saar, Germany;
5
Septomics Research Center, Jena University Hospital, Jena, Germany; Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena, Germany;
6
Institute of Anatomy, Medical Faculty, University Duisburg-Essen, Essen, Germany;
7
Clinical Microbiology, Department of Translational Medicine Malmö, Lund University, Malmö, Sweden;
8
Tumor Immunology Laboratory, LIFE-Center, Klinikum Grosshadern, Ludwig-Maximilians-University Munich, Munich, Germany; and.
9
Department of Anatomy, Charité-Universitätsmedizin Berlin, Berlin, Germany.
10
Septomics Research Center, Jena University Hospital, Jena, Germany; hortense.slevogt@med.uni-jena.de.

Abstract

In patients with chronic obstructive pulmonary disease (COPD), Moraxella catarrhalis infection of the lower airways is associated with chronic colonization and inflammation during stable disease and acute exacerbations. Chronic smoke exposure induces chronic inflammation and impairs mucociliary clearance, thus contributing to bacterial colonization of the lower airways in COPD patients. The human-specific carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 5, expressed in human airways, has been shown to contribute to epithelial colonization of CEACAM-binding pathogens. To investigate the impact of CEACAM5 expression on pulmonary M. catarrhalis colonization, we infected mice transgenic for human CEACAM5 (hCEACAM5) and wild type mice intratracheally with M. catarrhalis with or without preceding smoke exposure and analyzed bacterial colonization and local and systemic inflammation. Our results show that airway infection with M. catarrhalis accelerated acute local but not systemic inflammation, albeit independent of hCEACAM5 expression. Long-term smoke exposure alone or prior to M. catarrhalis infection did not contribute to increased local or systemic inflammation. No difference was found in pulmonary clearance of M. catarrhalis in hCEACAM5-transgenic mice compared with wild-type mice. Smoke exposure neither altered time nor extent of persistence of M. catarrhalis in the lungs of both genotypes. In conclusion, M. catarrhalis induced a local acute immune response in murine airways. Neither hCEACAM5 expression nor chronic smoke exposure nor a combination of both was sufficient as prerequisites for the establishment of chronic M. catarrhalis colonization. Our results demonstrate the difficulties in mirroring conditions of chronic airways colonization of M. catarrhalis in a murine model.

KEYWORDS:

CEACAM5; COPD; M. catarrhalis; chronic smoke exposure; mouse model

PMID:
26047639
DOI:
10.1152/ajplung.00265.2014
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Atypon
Loading ...
Support Center