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

Details

• Alternative Title:
  PLoS One
• Personal Author:
  Fatykhova, Diana ; Rabes, Anne ; Machnik, Christoph ; Guruprasad, Kunchur ; Pache, Florence ; Berg, Johanna ; Toennies, Mario ; Bauer, Torsten T. ; Schneider, Paul ; Schimek, Maria ; Eggeling, Stephan ; Mitchell, Timothy J. ; Mitchell, Andrea M. ; Hilker, Rolf ; Hain, Torsten ; Suttorp, Norbert ; Hippenstiel, Stefan ; Hocke, Andreas C. ; Opitz, Bastian
• Description:
  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.
• Subjects:
  Bacterial Proteins Caspase 1 Hemolysis Humans Inflammasomes Interleukin-1beta Lung Species Specificity Streptococcus Pneumoniae Streptolysins
• Source:
  PLoS One. 2015; 10(8).
• Pubmed ID:
  26317436
• Pubmed Central ID:
  PMC4552725
• Document Type:
  Journal Article
• Volume:
  10
• Issue:
  8
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:e4cddb39d1bf8aaea55346e6857857d320176ea8e107b6cf93a925194f4e9545
• Download URL:
  https://stacks.cdc.gov/view/cdc/34248/cdc_34248_DS1.pdf
• File Type:
  [PDF - 2.95 MB ]