Serotype 1 and 8 pneumococci evade sensing by Inflammasomes in human lung tissue

Diana Fatykhova, Anne Rabes, Christoph Machnik, Kunchur Guruprasad, Florence Pache, Johanna Berg, Mario Toennies, Torsten T Bauer, Paul Schneider, Maria Schimek, Stephan Eggeling, Timothy J Mitchell, Andrea M Mitchell, Rolf Hilker, Torsten Hain, Norbert Suttorp, Stefan Hippenstiel, Andreas C Hocke, Bastian Opitz

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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.

Original languageEnglish
Pages (from-to)e0137108
JournalPLoS ONE
Volume10
Issue number8
DOIs
Publication statusPublished - 28 Aug 2015

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