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Diversion of the host humoral response: a novel virulence mechanism of Haemophilus influenzae mediated via outer membrane vesicles.

Deknuydt, Florence LU ; Nordström, Therése LU and Riesbeck, Kristian LU orcid (2014) In Journal of Leukocyte Biology 95(6). p.983-991
Abstract
The respiratory tract pathogen Haemophilus influenzae frequently causes infections in humans. In parallel with all Gram-negative bacteria, H. influenzae has the capacity to release OMV. The production of these nanoparticles is an intriguing and partly unexplored phenomenon in pathogenesis. Here, we investigated how purified human peripheral blood B lymphocytes respond to OMV derived from unencapsulated, i.e., NTHi and the nonpathogenic Haemophilus parainfluenzae. We found that H. influenzae OMV directly interacted with the IgD BCR, as revealed by anti-IgD pAb and flow cytometry. Importantly, H. influenzae OMV-induced cellular activation via IgD BCR cross-linking and TLR9 resulted in a significant proliferative response. OMV isolated from... (More)
The respiratory tract pathogen Haemophilus influenzae frequently causes infections in humans. In parallel with all Gram-negative bacteria, H. influenzae has the capacity to release OMV. The production of these nanoparticles is an intriguing and partly unexplored phenomenon in pathogenesis. Here, we investigated how purified human peripheral blood B lymphocytes respond to OMV derived from unencapsulated, i.e., NTHi and the nonpathogenic Haemophilus parainfluenzae. We found that H. influenzae OMV directly interacted with the IgD BCR, as revealed by anti-IgD pAb and flow cytometry. Importantly, H. influenzae OMV-induced cellular activation via IgD BCR cross-linking and TLR9 resulted in a significant proliferative response. OMV isolated from the related species H. parainfluenzae did not, however, interact with B cells excluding that the effect by H. influenzae OMV was linked to common membrane components, such as the LOS. We also observed an up-regulation of the cell surface molecules CD69 and CD86, and an increased IgM and IgG secretion by B cells incubated with H. influenzae OMV. The Igs produced did not recognize H. influenzae, suggesting a polyclonal B cell activation. Interestingly, the density of the cell surface receptor TACI was increased in the presence of OMV that sensitized further the B cells to BAFF, resulting in an enhanced IgG class-switch. In conclusion, the ability of NTHi OMV to activate B cells in a T cell-independent manner may divert the adaptive humoral immune response that consequently promotes bacterial survival within the human host. (Less)
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author
; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Leukocyte Biology
volume
95
issue
6
pages
983 - 991
publisher
John Wiley & Sons Inc.
external identifiers
  • pmid:24550522
  • wos:000337289600014
  • scopus:84901700533
  • pmid:24550522
ISSN
1938-3673
DOI
10.1189/jlb.1013527
language
English
LU publication?
yes
id
a34fd4d1-ed1c-4903-bb5e-d02bec1f12bf (old id 4334466)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24550522?dopt=Abstract
date added to LUP
2016-04-01 10:31:40
date last changed
2022-01-26 00:05:36
@article{a34fd4d1-ed1c-4903-bb5e-d02bec1f12bf,
  abstract     = {{The respiratory tract pathogen Haemophilus influenzae frequently causes infections in humans. In parallel with all Gram-negative bacteria, H. influenzae has the capacity to release OMV. The production of these nanoparticles is an intriguing and partly unexplored phenomenon in pathogenesis. Here, we investigated how purified human peripheral blood B lymphocytes respond to OMV derived from unencapsulated, i.e., NTHi and the nonpathogenic Haemophilus parainfluenzae. We found that H. influenzae OMV directly interacted with the IgD BCR, as revealed by anti-IgD pAb and flow cytometry. Importantly, H. influenzae OMV-induced cellular activation via IgD BCR cross-linking and TLR9 resulted in a significant proliferative response. OMV isolated from the related species H. parainfluenzae did not, however, interact with B cells excluding that the effect by H. influenzae OMV was linked to common membrane components, such as the LOS. We also observed an up-regulation of the cell surface molecules CD69 and CD86, and an increased IgM and IgG secretion by B cells incubated with H. influenzae OMV. The Igs produced did not recognize H. influenzae, suggesting a polyclonal B cell activation. Interestingly, the density of the cell surface receptor TACI was increased in the presence of OMV that sensitized further the B cells to BAFF, resulting in an enhanced IgG class-switch. In conclusion, the ability of NTHi OMV to activate B cells in a T cell-independent manner may divert the adaptive humoral immune response that consequently promotes bacterial survival within the human host.}},
  author       = {{Deknuydt, Florence and Nordström, Therése and Riesbeck, Kristian}},
  issn         = {{1938-3673}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{983--991}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Journal of Leukocyte Biology}},
  title        = {{Diversion of the host humoral response: a novel virulence mechanism of Haemophilus influenzae mediated via outer membrane vesicles.}},
  url          = {{http://dx.doi.org/10.1189/jlb.1013527}},
  doi          = {{10.1189/jlb.1013527}},
  volume       = {{95}},
  year         = {{2014}},
}