Multicomponent Moraxella catarrhalis outer membrane vesicles induce an inflammatory response and are internalized by human epithelial cells.
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.
Medical Microbiology, Department of Laboratory Medicine Malmö, Lund University, Skåne University Hospital, Sweden.
Viveka
V
Schaar
Stefan P W
SP
de Vries
Maria Laura A
ML
Perez Vidakovics
Hester J
HJ
Bootsma
Lennart
L
Larsson
Peter W M
PW
Hermans
Anders
A
Bjartell
Matthias
M
Mörgelin
Kristian
K
Riesbeck
D018829:Adhesins, Bacterial / Q000276:immunology; D000818:Animals; D001422:Bacterial Adhesion; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000276:immunology / Q000382:microbiology* / Q000502:physiology; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D008168:Lung / Q000276:immunology; D021962:Membrane Microdomains / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D001936:Moraxella catarrhalis / Q000276:immunology* / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D020543:Proteome; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013194:Staining and Labeling; D051195:Toll-Like Receptor 2 / Q000276:immunology
D018829:Adhesins, Bacterial; D001425:Bacterial Outer Membrane Proteins; C439616:IgD-binding protein MID, Moraxella catarrhalis; D020543:Proteome; D051195:Toll-Like Receptor 2; D016650:Fluorescein-5-isothiocyanate