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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.

Author information

1
Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
2
Bioinformatics, Centre for Cellular and Molecular Biology, Hyderabad, Telangana, India.
3
Lungenklinik Heckeshorn, HELIOS Klinikum Emil von Behring, Walterhöferstrasse 11, 14165, Berlin, Germany.
4
Department for General and Thoracic Surgery, DRK Clinics, Drontheimer Strasse 39-40, 13359, Berlin, Germany.
5
Vivantes Klinikum Neukölln, Department for Thoracic Surgery, Berlin, Rudower Straße 48, 12351, Berlin, Germany.
6
Institute of Microbiology and Infection, School of Infection and Immunity, University of Birmingham, Birmingham, B15-2TT, United Kingdom.
7
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.
8
Institute of Medical Microbiology, Justus-Liebig University Giessen, Schubertstrasse 81, D-35392, Giessen, Germany.

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.

PMID:
26317436
PMCID:
PMC4552725
DOI:
10.1371/journal.pone.0137108
[Indexed for MEDLINE]
Free PMC Article

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