title: The interrelationship between phagocytosis, autophagy and formation of neutrophil extracellular traps following infection of human neutrophils by Streptococcus pneumoniae.
abstract: Neutrophils play an important role in the innate immune response to infection with Streptococcus pneumoniae, the pneumococcus. Pneumococci are phagocytosed by neutrophils and undergo killing after ingestion. Other cellular processes may also be induced, including autophagy and the formation of neutrophil extracellular traps (NETs), which may play a role in bacterial eradication. We set out to determine how these different processes interacted following pneumococcal infection of neutrophils, and the role of the major pneumococcal toxin pneumolysin in these various pathways. We found that pneumococci induced autophagy in neutrophils in a type III phosphatidylinositol-3 kinase dependent fashion that also required the autophagy gene Atg5. Pneumolysin did not affect this process. Phagocytosis was inhibited by pneumolysin but enhanced by autophagy, while killing was accelerated by pneumolysin but inhibited by autophagy. Pneumococci induced extensive NET formation in neutrophils that was not influenced by pneumolysin but was critically dependent on autophagy. While pneumolysin did not affect NET formation, it had a potent inhibitory effect on bacterial trapping within NETs. These findings show a complex interaction between phagocytosis, killing, autophagy and NET formation in neutrophils following pneumococcal infection that contribute to host defence against this pathogen.
authors.affiliation: Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow Biomedical research Centre, Glasgow, UK.
authors.forename: Ihsan
authors.initials: I
authors.lastname: Ullah
authors.affiliation: Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow Biomedical research Centre, Glasgow, UK.
authors.forename: Neil D
authors.initials: ND
authors.lastname: Ritchie
authors.affiliation: Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow Biomedical research Centre, Glasgow, UK.
authors.forename: Tom J
authors.initials: TJ
authors.lastname: Evans
mesh_terms: D001343:Autophagy; D000071187:Autophagy-Related Protein 5 / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000276:immunology; D001433:Bacteriolysis; D002478:Cells, Cultured; D065206:Extracellular Traps / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D018375:Neutrophil Activation; D009504:Neutrophils / Q000276:immunology*; D010587:Phagocytosis; D011008:Pneumococcal Infections / Q000276:immunology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013296:Streptococcus pneumoniae / Q000276:immunology*; D013301:Streptolysins / Q000276:immunology*
chemical_list: C502778:ATG5 protein, human; D000071187:Autophagy-Related Protein 5; D001426:Bacterial Proteins; D017382:Reactive Oxygen Species; D013301:Streptolysins; C032290:plY protein, Streptococcus pneumoniae
keywords: Autophagy; Streptococcus pneumoniae; bacterial killing; neutrophil extracellular trap; pneumolysin