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Streptococcus pneumoniae evades human dendritic cell surveillance by pneumolysin expression

Dendritic cells (DCs) protect the respiratory epithelium via induction of innate immune responses and priming of naïve T cells during the initiation of adaptive immunity. Streptococcus pneumoniae, a commonly carried asymptomatic member of the human nasopharyngeal microflora, can cause invasive and i...

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Autores principales: Littmann, Marie, Albiger, Barbara, Frentzen, Anne, Normark, Staffan, Henriques-Normark, Birgitta, Plant, Laura
Formato: Online Artículo Texto
Lenguaje:English
Publicado: WILEY-VCH Verlag 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3378134/
https://www.ncbi.nlm.nih.gov/pubmed/20049723
http://dx.doi.org/10.1002/emmm.200900025
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author Littmann, Marie
Albiger, Barbara
Frentzen, Anne
Normark, Staffan
Henriques-Normark, Birgitta
Plant, Laura
author_facet Littmann, Marie
Albiger, Barbara
Frentzen, Anne
Normark, Staffan
Henriques-Normark, Birgitta
Plant, Laura
author_sort Littmann, Marie
collection PubMed
description Dendritic cells (DCs) protect the respiratory epithelium via induction of innate immune responses and priming of naïve 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.
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spelling pubmed-33781342012-09-17 Streptococcus pneumoniae evades human dendritic cell surveillance by pneumolysin expression Littmann, Marie Albiger, Barbara Frentzen, Anne Normark, Staffan Henriques-Normark, Birgitta Plant, Laura EMBO Mol Med Research Articles Dendritic cells (DCs) protect the respiratory epithelium via induction of innate immune responses and priming of naïve 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. WILEY-VCH Verlag 2009-07 /pmc/articles/PMC3378134/ /pubmed/20049723 http://dx.doi.org/10.1002/emmm.200900025 Text en Copyright © 2009 EMBO Molecular Medicine
spellingShingle Research Articles
Littmann, Marie
Albiger, Barbara
Frentzen, Anne
Normark, Staffan
Henriques-Normark, Birgitta
Plant, Laura
Streptococcus pneumoniae evades human dendritic cell surveillance by pneumolysin expression
title Streptococcus pneumoniae evades human dendritic cell surveillance by pneumolysin expression
title_full Streptococcus pneumoniae evades human dendritic cell surveillance by pneumolysin expression
title_fullStr Streptococcus pneumoniae evades human dendritic cell surveillance by pneumolysin expression
title_full_unstemmed Streptococcus pneumoniae evades human dendritic cell surveillance by pneumolysin expression
title_short Streptococcus pneumoniae evades human dendritic cell surveillance by pneumolysin expression
title_sort streptococcus pneumoniae evades human dendritic cell surveillance by pneumolysin expression
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3378134/
https://www.ncbi.nlm.nih.gov/pubmed/20049723
http://dx.doi.org/10.1002/emmm.200900025
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