Streptococcus pneumoniae evades human dendritic cell surveillance by pneumolysin expression

Research output: Contribution to journalArticle

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.

Details

Authors
  • Marie Littmann
  • Barbara Albiger
  • Anne Frentzen
  • Staffan Normark
  • Birgitta Henriques-Normark
  • Laura Plant
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell and Molecular Biology

Keywords

  • pneumococci, pneumolysin, inflammatory response, apoptosis, dendritic cells
Original languageEnglish
Pages (from-to)211-222
JournalEMBO Molecular Medicine
Volume1
Issue number4
Publication statusPublished - 2009
Publication categoryResearch
Peer-reviewedYes