Multicomponent Moraxella catarrhalis outer membrane vesicles induce an inflammatory response and are internalized by human epithelial cells

• Published in: Cellular microbiology Vol. 13; no. 3; pp. 432 - 449
• Main Authors: Schaar, Viveka, de Vries, Stefan P.W, Perez Vidakovics, Maria Laura A, Bootsma, Hester J, Larsson, Lennart, Hermans, Peter W.M, Bjartell, Anders, Mörgelin, Matthias, Riesbeck, Kristian
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.03.2011; Hindawi Limited
• Subjects: Active transport; Adhesins; Adhesins, Bacterial - immunology; Alveoli; Animals; Bacterial Adhesion; Bacterial Outer Membrane Proteins - immunology; Biologi; Biological Sciences; Children; Chronic obstructive pulmonary disease; Electrophoresis, Polyacrylamide Gel; Enzyme-Linked Immunosorbent Assay; Epithelial cells; Epithelial Cells - immunology; Epithelial Cells - microbiology; Epithelial Cells - physiology; Flow Cytometry; Fluorescein-5-isothiocyanate - metabolism; Humans; Immune response; Inflammation; Lipid rafts; Lung - immunology; Mass spectroscopy; Membrane Microdomains - metabolism; Membrane vesicles; Mice; Mice, Inbred BALB C; Microbiology; Microscopy, Electron; Mikrobiologi; Moraxella (Branhamella) catarrhalis - immunology; Moraxella (Branhamella) catarrhalis - metabolism; Moraxella catarrhalis; Natural Sciences; Naturvetenskap; Otitis media; Outer membranes; Pathogens; Polymerase Chain Reaction; Proteome; proteomics; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Staining and Labeling; TLR2 protein; Toll-Like Receptor 2 - immunology; Toll-like receptors; virulence factors
• ISSN: 1462-5814; 1462-5822
• DOI: 10.1111/j.1462-5822.2010.01546.x

Moraxella catarrhalis is an emerging human respiratory pathogen in patients with chronic obstructive pulmonary disease (COPD) and in children with acute otitis media. The specific secretion machinery known as outer membrane vesicles (OMVs) is a mechanism by which Gram-negative pathogens interact with host cells during infection. We identified 57 proteins in M. catarrhalis OMVs using a proteomics approach combining two-dimensional SDS-PAGE and MALDI-TOF mass spectrometry analysis. The OMVs contained known surface proteins such as ubiquitous surface proteins (Usp) A1/A2, and Moraxella IgD-binding protein (MID). Most of the proteins are adhesins/virulence factors triggering the immune response, but also aid bacteria to evade the host defence. FITC-stained OMVs bound to lipid raft domains in alveolar epithelial cells and were internalized after interaction with Toll-like receptor 2 (TLR2), suggesting a delivery to the host tissue of a large and complex group of OMV-attributed proteins. Interestingly, OMVs modulated the pro-inflammatory response in epithelial cells, and UspA1-bearing OMVs were found to specifically downregulate the reaction. When mice were exposed to OMVs, a pulmonary inflammation was clearly seen. Our findings indicate that Moraxella OMVs are highly biologically active, transport main bacterial virulence factors and may modulate the epithelial pro-inflammatory response.