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

Vidakovics, Maria Laura A Perez; Jendholm, Johan; Mörgelin, Matthias LU ; Månsson, Anne LU ; Larsson, Christer LU ; Cardell, Lars-Olaf LU and Riesbeck, Kristian LU (2010) In PLoS Pathogens 6(1).
Abstract
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... (More)
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. (Less)
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Contribution to journal
publication status
published
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in
PLoS Pathogens
volume
6
issue
1
publisher
Public Library of Science
external identifiers
  • wos:000274227100015
  • pmid:20090836
  • scopus:77649207615
ISSN
1553-7366
DOI
10.1371/journal.ppat.1000724
language
English
LU publication?
yes
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2df30381-ffed-4b4a-8d0a-6a0fc415a127 (old id 1540720)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20090836?dopt=Abstract
date added to LUP
2010-02-04 15:45:16
date last changed
2018-07-15 03:08:49
@article{2df30381-ffed-4b4a-8d0a-6a0fc415a127,
  abstract     = {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.},
  author       = {Vidakovics, Maria Laura A Perez and Jendholm, Johan and Mörgelin, Matthias and Månsson, Anne and Larsson, Christer and Cardell, Lars-Olaf and Riesbeck, Kristian},
  issn         = {1553-7366},
  language     = {eng},
  number       = {1},
  publisher    = {Public Library of Science},
  series       = {PLoS Pathogens},
  title        = {B cell activation by outer membrane vesicles--a novel virulence mechanism.},
  url          = {http://dx.doi.org/10.1371/journal.ppat.1000724},
  volume       = {6},
  year         = {2010},
}