RRC ID 51962
Author Domon H, Oda M, Maekawa T, Nagai K, Takeda W, Terao Y.
Title Streptococcus pneumoniae disrupts pulmonary immune defence via elastase release following pneumolysin-dependent neutrophil lysis.
Journal Sci Rep
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. P2X7 receptor, 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.
Volume 6
Pages 38013
Published 2016-11-28
DOI 10.1038/srep38013
PII srep38013
PMID 27892542
PMC PMC5125098
MeSH Alveolar Epithelial Cells Animals Bacterial Proteins / genetics Bacterial Proteins / metabolism Bacterial Proteins / toxicity Cell Adhesion Cell Death Cell Line Host-Pathogen Interactions / immunology* Humans Leukocyte Elastase / metabolism* Macrophages / microbiology Macrophages / pathology Mice Neutrophils / drug effects Neutrophils / microbiology Neutrophils / pathology* Phagocytosis / physiology Receptors, Purinergic P2X7 / metabolism Streptococcus pneumoniae / pathogenicity* Streptolysins / genetics Streptolysins / metabolism* Streptolysins / toxicity
IF 3.998
Times Cited 16
Human and Animal Cells RAW 264(RCB0535) A549