Serotype 1 and 8 Pneumococci Evade Sensing by Inflammasomes in Human Lung Tissue

PLoS One. 2015 Aug 28;10(8):e0137108. doi: 10.1371/journal.pone.0137108. eCollection 2015.

Abstract

Streptococcus pneumoniae is a major cause of pneumonia, sepsis and meningitis. The pore-forming toxin pneumolysin is a key virulence factor of S. pneumoniae, which can be sensed by the NLRP3 inflammasome. Among the over 90 serotypes, serotype 1 pneumococci (particularly MLST306) have emerged across the globe as a major cause of invasive disease. The cause for its particularity is, however, incompletely understood. We therefore examined pneumococcal infection in human cells and a human lung organ culture system mimicking infection of the lower respiratory tract. We demonstrate that different pneumococcal serotypes differentially activate inflammasome-dependent IL-1β production in human lung tissue and cells. Whereas serotype 2, 3, 6B, 9N pneumococci expressing fully haemolytic pneumolysins activate NLRP3 inflammasome-dependent responses, serotype 1 and 8 strains expressing non-haemolytic toxins are poor activators of IL-1β production. Accordingly, purified haemolytic pneumolysin but not serotype 1-associated non-haemolytic toxin activates strong IL-1β production in human lungs. Our data suggest that the evasion of inflammasome-dependent innate immune responses by serotype 1 pneumococci might contribute to their ability to cause invasive diseases in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / metabolism
  • Caspase 1 / metabolism
  • Hemolysis
  • Humans
  • Inflammasomes / metabolism*
  • Interleukin-1beta / biosynthesis
  • Lung / cytology
  • Lung / immunology
  • Lung / metabolism*
  • Lung / microbiology*
  • Species Specificity
  • Streptococcus pneumoniae / classification
  • Streptococcus pneumoniae / immunology
  • Streptococcus pneumoniae / metabolism
  • Streptococcus pneumoniae / physiology*
  • Streptolysins / metabolism

Substances

  • Bacterial Proteins
  • Inflammasomes
  • Interleukin-1beta
  • Streptolysins
  • plY protein, Streptococcus pneumoniae
  • Caspase 1

Grant support

This work was supported by the Deutsche Forschungsgemeinschaft (www.dfg.de)(GRK1673/B5 to A.R. and B.O., OP 86/7-2 to B.O., SFB-TR84 project B01 to T.H. and to N.S., project Z1a to A.C.H., project B06 to A.C.H and S.H., and project A01/A05 to B.O.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.