PMID- 20049723
OWN - NLM
STAT- MEDLINE
DCOM- 20100310
LR  - 20211020
IS  - 1757-4684 (Electronic)
IS  - 1757-4676 (Print)
IS  - 1757-4676 (Linking)
VI  - 1
IP  - 4
DP  - 2009 Jul
TI  - Streptococcus pneumoniae evades human dendritic cell surveillance by pneumolysin 
      expression.
PG  - 211-22
LID - 10.1002/emmm.200900025 [doi]
AB  - 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.
FAU - Littmann, Marie
AU  - Littmann M
AD  - Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Nobels 
      vag 16, Stockholm SE-171 77, Sweden.
FAU - Albiger, Barbara
AU  - Albiger B
FAU - Frentzen, Anne
AU  - Frentzen A
FAU - Normark, Staffan
AU  - Normark S
FAU - Henriques-Normark, Birgitta
AU  - Henriques-Normark B
FAU - Plant, Laura
AU  - Plant L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - EMBO Mol Med
JT  - EMBO molecular medicine
JID - 101487380
RN  - 0 (Bacterial Proteins)
RN  - 0 (Cytokines)
RN  - 0 (Streptolysins)
RN  - 0 (plY protein, Streptococcus pneumoniae)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Bacterial Capsules/genetics/metabolism
MH  - Bacterial Proteins/genetics/metabolism
MH  - Caspases/immunology
MH  - Cells, Cultured
MH  - Cytokines/immunology
MH  - Dendritic Cells/cytology/*immunology/*microbiology
MH  - *Gene Expression Regulation, Bacterial
MH  - Humans
MH  - Mice
MH  - Mutation
MH  - Pneumococcal Infections/*genetics/immunology/metabolism
MH  - Serotyping
MH  - Streptococcus pneumoniae/classification/genetics/*pathogenicity
MH  - Streptolysins/*genetics/metabolism
PMC - PMC3378134
EDAT- 2010/01/06 06:00
MHDA- 2010/03/11 06:00
PMCR- 2009/07/01
CRDT- 2010/01/06 06:00
PHST- 2010/01/06 06:00 [entrez]
PHST- 2010/01/06 06:00 [pubmed]
PHST- 2010/03/11 06:00 [medline]
PHST- 2009/07/01 00:00 [pmc-release]
AID - 10.1002/emmm.200900025 [doi]
PST - ppublish
SO  - EMBO Mol Med. 2009 Jul;1(4):211-22. doi: 10.1002/emmm.200900025.