title: Streptococcus pneumoniae disrupts pulmonary immune defence via elastase release following pneumolysin-dependent neutrophil lysis.
abstract: Streptococcus pneumoniae is a leading cause of bacterial pneumonia and is the principal cause of morbidity and mortality worldwide. Previous studies suggested that excessive activation of neutrophils results in the release of neutrophil elastase, which contributes to lung injury in severe pneumonia. Although both pneumococcal virulence factors and neutrophil elastase contribute to the development and progression of pneumonia, there are no studies analysing relationships between these factors. Here, we showed that pneumolysin, a pneumococcal pore-forming toxin, induced cell lysis in primary isolated human neutrophils, leading to the release of neutrophil elastase. Pneumolysin exerted minimal cytotoxicity against alveolar epithelial cells and macrophages, whereas neutrophil elastase induced detachment of alveolar epithelial cells and impaired phagocytic activity in macrophages. Additionally, activation of neutrophil elastase did not exert bactericidal activity against S. pneumoniae in vitro. P2X7receptor, which belongs to a family of purinergic receptors, was involved in pneumolysin-induced cell lysis. These findings suggested that infiltrated neutrophils are the primary target cells of pneumolysin, and that S. pneumoniae exploits neutrophil-elastase leakage to induce the disruption of pulmonary immune defences, thereby causing lung injury.
authors.affiliation: Division of Microbiology and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, Chuo-ku, Niigata, Japan.|Research Center for Advanced Oral Science, Niigata University, Graduate School of Medical and Dental Sciences, Chuo-ku, Niigata, Japan.
authors.forename: Hisanori
authors.initials: H
authors.lastname: Domon
authors.affiliation: Division of Microbiology and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, Chuo-ku, Niigata, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Oda
authors.affiliation: Division of Microbiology and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, Chuo-ku, Niigata, Japan.|Research Center for Advanced Oral Science, Niigata University, Graduate School of Medical and Dental Sciences, Chuo-ku, Niigata, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Maekawa
authors.affiliation: Division of Microbiology and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, Chuo-ku, Niigata, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Nagai
authors.affiliation: Faculty of Dentistry, Niigata University, Chuo-ku, Niigata, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Takeda
authors.affiliation: Division of Microbiology and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, Chuo-ku, Niigata, Japan.|Research Center for Advanced Oral Science, Niigata University, Graduate School of Medical and Dental Sciences, Chuo-ku, Niigata, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Terao
mesh_terms: D056809:Alveolar Epithelial Cells; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism / Q000633:toxicity; D002448:Cell Adhesion; D016923:Cell Death; D002460:Cell Line; D054884:Host-Pathogen Interactions / Q000276:immunology*; D006801:Humans; D019272:Leukocyte Elastase / Q000378:metabolism*; D008264:Macrophages / Q000382:microbiology / Q000473:pathology; D051379:Mice; D009504:Neutrophils / Q000187:drug effects / Q000382:microbiology / Q000473:pathology*; D010587:Phagocytosis / Q000502:physiology; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism; D013296:Streptococcus pneumoniae / Q000472:pathogenicity*; D013301:Streptolysins / Q000235:genetics / Q000378:metabolism* / Q000633:toxicity
chemical_list: D001426:Bacterial Proteins; C546468:P2RX7 protein, human; D058486:Receptors, Purinergic P2X7; D013301:Streptolysins; C032290:plY protein, Streptococcus pneumoniae; D019272:Leukocyte Elastase