title: Moraxella catarrhalis induces an immune response in the murine lung that is independent of human CEACAM5 expression and long-term smoke exposure.
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.
authors.affiliation: Department of Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany;
authors.forename: Birgitt
authors.initials: B
authors.lastname: Gutbier
authors.affiliation: Department of Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany; Septomics Research Center, Jena University Hospital, Jena, Germany;
authors.forename: Katja
authors.initials: K
authors.lastname: Fischer
authors.affiliation: Department of Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany;
authors.forename: Jan-Moritz
authors.initials: JM
authors.lastname: Doehn
authors.affiliation: Septomics Research Center, Jena University Hospital, Jena, Germany;
authors.forename: Carolin
authors.initials: C
authors.lastname: von Lachner
authors.affiliation: Department of Internal Medicine V-Pulmonology, Allergology, Respiratory Intensive Care Medicine, University of the Saarland, Homburg Saar, Germany;
authors.forename: Christian
authors.initials: C
authors.lastname: Herr
authors.affiliation: Septomics Research Center, Jena University Hospital, Jena, Germany; Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena, Germany;
authors.forename: Esther
authors.initials: E
authors.lastname: Klaile
authors.affiliation: Septomics Research Center, Jena University Hospital, Jena, Germany;
authors.forename: Ursula
authors.initials: U
authors.lastname: Frischmann
authors.affiliation: Institute of Anatomy, Medical Faculty, University Duisburg-Essen, Essen, Germany;
authors.forename: Bernhard B
authors.initials: BB
authors.lastname: Singer
authors.affiliation: Clinical Microbiology, Department of Translational Medicine Malmö, Lund University, Malmö, Sweden;
authors.forename: Kristian
authors.initials: K
authors.lastname: Riesbeck
authors.affiliation: Tumor Immunology Laboratory, LIFE-Center, Klinikum Grosshadern, Ludwig-Maximilians-University Munich, Munich, Germany; and.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Zimmermann
authors.affiliation: Department of Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany;
authors.forename: Norbert
authors.initials: N
authors.lastname: Suttorp
authors.affiliation: Department of Anatomy, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Bachmann
authors.affiliation: Department of Internal Medicine V-Pulmonology, Allergology, Respiratory Intensive Care Medicine, University of the Saarland, Homburg Saar, Germany;
authors.forename: Robert
authors.initials: R
authors.lastname: Bals
authors.affiliation: Department of Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany;
authors.forename: Martin
authors.initials: M
authors.lastname: Witzenrath
authors.affiliation: Septomics Research Center, Jena University Hospital, Jena, Germany; hortense.slevogt@med.uni-jena.de.
authors.forename: Hortense
authors.initials: H
authors.lastname: Slevogt
mesh_terms: D000818:Animals; D002272:Carcinoembryonic Antigen / Q000235:genetics / Q000378:metabolism*; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D008168:Lung / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D001936:Moraxella catarrhalis / Q000276:immunology*; D045828:Moraxellaceae Infections / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D009079:Mucociliary Clearance; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000276:immunology / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D012907:Smoking / Q000276:immunology / Q000378:metabolism
chemical_list: C527875:CEACAM5 protein, human; D002272:Carcinoembryonic Antigen; D058851:GPI-Linked Proteins
keywords: CEACAM5; COPD; M. catarrhalis; chronic smoke exposure; mouse model