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

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

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Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
Bioinformatics, Centre for Cellular and Molecular Biology, Hyderabad, Telangana, India.
Lungenklinik Heckeshorn, HELIOS Klinikum Emil von Behring, Walterhöferstrasse 11, 14165, Berlin, Germany.
Department for General and Thoracic Surgery, DRK Clinics, Drontheimer Strasse 39-40, 13359, Berlin, Germany.
Vivantes Klinikum Neukölln, Department for Thoracic Surgery, Berlin, Rudower Straße 48, 12351, Berlin, Germany.
Institute of Microbiology and Infection, School of Infection and Immunity, University of Birmingham, Birmingham, B15-2TT, United Kingdom.
Institute of Medical Microbiology, Justus-Liebig University Giessen, Schubertstrasse 81, D-35392, Giessen, Germany; Department of Bioinformatics and Systems Biology, Justus-Liebig University Giessen, Heinrich-Buff-Ring 58, D-35392, Giessen, Germany.
Institute of Medical Microbiology, Justus-Liebig University Giessen, Schubertstrasse 81, D-35392, Giessen, Germany.


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.

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