• Open Access

Streptococcus pneumoniae evades human dendritic cell surveillance by pneumolysin expression

Authors

  • Marie Littmann,

    1. Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Nobels väg 16, Stockholm SE-171 77, Sweden
    2. Department of Bacteriology, Swedish Institute for Infectious Disease Control, Nobels väg 18, Solna SE-171 82, Sweden
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  • Barbara Albiger,

    1. Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Nobels väg 16, Stockholm SE-171 77, Sweden
    2. Department of Laboratory Medicine, Medical Microbiology, Malmö University Hospital, Malmö SE-205 02, Sweden
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  • Anne Frentzen,

    1. Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Nobels väg 16, Stockholm SE-171 77, Sweden
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  • Staffan Normark,

    1. Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Nobels väg 16, Stockholm SE-171 77, Sweden
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  • Birgitta Henriques-Normark,

    1. Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Nobels väg 16, Stockholm SE-171 77, Sweden
    2. Department of Bacteriology, Swedish Institute for Infectious Disease Control, Nobels väg 18, Solna SE-171 82, Sweden
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  • Laura Plant

    Corresponding author
    1. Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Nobels väg 16, Stockholm SE-171 77, Sweden
    • Tel: (+46) 8 524 86312; Fax: (+46) 8 304 276
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Abstract

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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