Advanced

Streptococcus pneumoniae evades human dendritic cell surveillance by pneumolysin expression

Littmann, Marie; Albiger, Barbara LU ; Frentzen, Anne; Normark, Staffan; Henriques-Normark, Birgitta and Plant, Laura (2009) In EMBO Molecular Medicine 1(4). p.211-222
Abstract
Dendritic cells (DCs) protect the respiratory epithelium via induction of innate immune responses and priming of naive T cells during the initiation of adaptive immunity. Streptococcus pneumoniae, a commonly carried asymptomatic member of the human nasopharyngeal microflora, can cause invasive and inflammatory diseases and the cholesterol-dependent cytotoxin pneumolysin is a major pneumococcal virulence factor implicated in compounding tissue damage and mediating inflammatory responses. While most studies examining the impact of pneumolysin have been based on murine models, we have focused this study on human DC responses. We show that expression of haemolytic pneumolysin inhibits human DC maturation, induction of proinflammatory cytokines... (More)
Dendritic cells (DCs) protect the respiratory epithelium via induction of innate immune responses and priming of naive T cells during the initiation of adaptive immunity. Streptococcus pneumoniae, a commonly carried asymptomatic member of the human nasopharyngeal microflora, can cause invasive and inflammatory diseases and the cholesterol-dependent cytotoxin pneumolysin is a major pneumococcal virulence factor implicated in compounding tissue damage and mediating inflammatory responses. While most studies examining the impact of pneumolysin have been based on murine models, we have focused this study on human DC responses. We show that expression of haemolytic pneumolysin inhibits human DC maturation, induction of proinflammatory cytokines and activation of the inflammasome. Furthermore, intracellular production of pneumolysin induces caspase-dependent apoptosis in infected DCs. Similarly, clinical isolates with non-haemolytic pneumolysin were more proinflammatory and caused less apoptosis compared to clonally related strains with active pneumolysin. This study describes a novel role of pneumolysin in the evasion of human DC surveillance that could have a profound clinical impact upon inflammatory disease progression and highlights the need to study human responses to human-specific pathogens. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
pneumococci, pneumolysin, inflammatory response, apoptosis, dendritic cells
in
EMBO Molecular Medicine
volume
1
issue
4
pages
211 - 222
publisher
Federation of European Neuroscience Societies and Blackwell Publishing Ltd
external identifiers
  • wos:000273563200005
  • scopus:77952584658
ISSN
1757-4684
DOI
10.1002/emmm.200900025
language
English
LU publication?
yes
id
0d8e53bb-6b10-48d8-afac-797c9bd9ef8a (old id 1546646)
date added to LUP
2010-02-25 14:07:36
date last changed
2017-09-17 04:58:17
@article{0d8e53bb-6b10-48d8-afac-797c9bd9ef8a,
  abstract     = {Dendritic cells (DCs) protect the respiratory epithelium via induction of innate immune responses and priming of naive T cells during the initiation of adaptive immunity. Streptococcus pneumoniae, a commonly carried asymptomatic member of the human nasopharyngeal microflora, can cause invasive and inflammatory diseases and the cholesterol-dependent cytotoxin pneumolysin is a major pneumococcal virulence factor implicated in compounding tissue damage and mediating inflammatory responses. While most studies examining the impact of pneumolysin have been based on murine models, we have focused this study on human DC responses. We show that expression of haemolytic pneumolysin inhibits human DC maturation, induction of proinflammatory cytokines and activation of the inflammasome. Furthermore, intracellular production of pneumolysin induces caspase-dependent apoptosis in infected DCs. Similarly, clinical isolates with non-haemolytic pneumolysin were more proinflammatory and caused less apoptosis compared to clonally related strains with active pneumolysin. This study describes a novel role of pneumolysin in the evasion of human DC surveillance that could have a profound clinical impact upon inflammatory disease progression and highlights the need to study human responses to human-specific pathogens.},
  author       = {Littmann, Marie and Albiger, Barbara and Frentzen, Anne and Normark, Staffan and Henriques-Normark, Birgitta and Plant, Laura},
  issn         = {1757-4684},
  keyword      = {pneumococci,pneumolysin,inflammatory response,apoptosis,dendritic cells},
  language     = {eng},
  number       = {4},
  pages        = {211--222},
  publisher    = {Federation of European Neuroscience Societies and Blackwell Publishing Ltd},
  series       = {EMBO Molecular Medicine},
  title        = {Streptococcus pneumoniae evades human dendritic cell surveillance by pneumolysin expression},
  url          = {http://dx.doi.org/10.1002/emmm.200900025},
  volume       = {1},
  year         = {2009},
}