B cell activation by outer membrane vesicles--a novel virulence mechanism

• Published in: PLoS pathogens Vol. 6; no. 1; p. e1000724
• Main Authors: Vidakovics, Maria Laura A Perez, Jendholm, Johan, Mörgelin, Matthias, Månsson, Anne, Larsson, Christer, Cardell, Lars-Olaf, Riesbeck, Kristian
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.01.2010; Public Library of Science (PLoS)
• Subjects: Adhesins, Bacterial - immunology; Amino acids; B cells; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; Bacteria; Basic Medicine; Blotting, Western; Branhamella catarrhalis; Cell Membrane - immunology; Cell Membrane - metabolism; Cell Separation; Child; Child, Preschool; Chronic obstructive pulmonary disease; CpG Islands - immunology; Ear diseases; Electrophoresis, Polyacrylamide Gel; Enzyme-Linked Immunosorbent Assay; Experiments; Flow Cytometry; Gas vesicles; Gram-negative bacteria; Health aspects; Humans; Immune system; Immunoglobulin D - immunology; Immunology; Immunology/Innate Immunity; Infectious Diseases/Bacterial Infections; Lymphocyte Activation - immunology; Medical and Health Sciences; Medicin och hälsovetenskap; Medicinska och farmaceutiska grundvetenskaper; Membrane Microdomains - immunology; Membrane Microdomains - metabolism; Microbiology; Microbiology in the medical area; Microbiology/Innate Immunity; Microbiology/Medical Microbiology; Microscopy, Confocal; Microscopy, Electron, Transmission; Microscopy, Fluorescence; Mikrobiologi inom det medicinska området; Moraxella (Branhamella) catarrhalis - immunology; Moraxella (Branhamella) catarrhalis - pathogenicity; Moraxella catarrhalis; Moraxellaceae Infections - immunology; Palatine Tonsil - immunology; Physiological aspects; Proteins; R&D; Receptors, Antigen, B-Cell - immunology; Research & development; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction - immunology; Sinusitis - immunology; Sinusitis - microbiology; Statistical analysis; T cell receptors; Virulence; Virulence (Microbiology); Sweden
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1000724

Secretion of outer membrane vesicles (OMV) is an intriguing phenomenon of Gram-negative bacteria and has been suggested to play a role as virulence factors. The respiratory pathogens Moraxella catarrhalis reside in tonsils adjacent to B cells, and we have previously shown that M. catarrhalis induce a T cell independent B cell response by the immunoglobulin (Ig) D-binding superantigen MID. Here we demonstrate that Moraxella are endocytosed and killed by human tonsillar B cells, whereas OMV have the potential to interact and activate B cells leading to bacterial rescue. The B cell response induced by OMV begins with IgD B cell receptor (BCR) clustering and Ca(2+) mobilization followed by BCR internalization. In addition to IgD BCR, TLR9 and TLR2 were found to colocalize in lipid raft motifs after exposure to OMV. Two components of the OMV, i.e., MID and unmethylated CpG-DNA motifs, were found to be critical for B cell activation. OMV containing MID bound to and activated tonsillar CD19(+) IgD(+) lymphocytes resulting in IL-6 and IgM production in addition to increased surface marker density (HLA-DR, CD45, CD64, and CD86), whereas MID-deficient OMV failed to induce B cell activation. DNA associated with OMV induced full B cell activation by signaling through TLR9. Importantly, this concept was verified in vivo, as OMV equipped with MID and DNA were found in a 9-year old patient suffering from Moraxella sinusitis. In conclusion, Moraxella avoid direct interaction with host B cells by redirecting the adaptive humoral immune response using its superantigen-bearing OMV as decoys.