title: Serotype 1 and 8 Pneumococci Evade Sensing by Inflammasomes in Human Lung Tissue.
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.
authors: Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
authors: Diana
authors: D
authors: Fatykhova
authors: Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
authors: Anne
authors: A
authors: Rabes
authors: Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
authors: Christoph
authors: C
authors: Machnik
authors: Bioinformatics, Centre for Cellular and Molecular Biology, Hyderabad, Telangana, India.
authors: Kunchur
authors: K
authors: Guruprasad
authors: Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
authors: Florence
authors: F
authors: Pache
authors: Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
authors: Johanna
authors: J
authors: Berg
authors: Lungenklinik Heckeshorn, HELIOS Klinikum Emil von Behring, Walterhöferstrasse 11, 14165, Berlin, Germany.
authors: Mario
authors: M
authors: Toennies
authors: Lungenklinik Heckeshorn, HELIOS Klinikum Emil von Behring, Walterhöferstrasse 11, 14165, Berlin, Germany.
authors: Torsten T
authors: TT
authors: Bauer
authors: Department for General and Thoracic Surgery, DRK Clinics, Drontheimer Strasse 39-40, 13359, Berlin, Germany.
authors: Paul
authors: P
authors: Schneider
authors: Vivantes Klinikum Neukölln, Department for Thoracic Surgery, Berlin, Rudower Straße 48, 12351, Berlin, Germany.
authors: Maria
authors: M
authors: Schimek
authors: Vivantes Klinikum Neukölln, Department for Thoracic Surgery, Berlin, Rudower Straße 48, 12351, Berlin, Germany.
authors: Stephan
authors: S
authors: Eggeling
authors: Institute of Microbiology and Infection, School of Infection and Immunity, University of Birmingham, Birmingham, B15-2TT, United Kingdom.
authors: Timothy J
authors: TJ
authors: Mitchell
authors: Institute of Microbiology and Infection, School of Infection and Immunity, University of Birmingham, Birmingham, B15-2TT, United Kingdom.
authors: Andrea M
authors: AM
authors: Mitchell
authors: 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.
authors: Rolf
authors: R
authors: Hilker
authors: Institute of Medical Microbiology, Justus-Liebig University Giessen, Schubertstrasse 81, D-35392, Giessen, Germany.
authors: Torsten
authors: T
authors: Hain
authors: Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
authors: Norbert
authors: N
authors: Suttorp
authors: Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
authors: Stefan
authors: S
authors: Hippenstiel
authors: Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
authors: Andreas C
authors: AC
authors: Hocke
authors: Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
authors: Bastian
authors: B
authors: Opitz
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism; D020170:Caspase 1 / Q000378:metabolism; D006461:Hemolysis; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D053583:Interleukin-1beta / Q000096:biosynthesis; D008168:Lung / Q000166:cytology / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology*; D013045:Species Specificity; D013296:Streptococcus pneumoniae / Q000145:classification / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D013301:Streptolysins / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; D013301:Streptolysins; C032290:plY protein, Streptococcus pneumoniae; D020170:Caspase 1