title: Streptococcus pneumoniae autolysis prevents phagocytosis and production of phagocyte-activating cytokines.
abstract: Streptococcus pneumoniae is a major pathogen in humans. The pathogenicity of this organism is related to its many virulence factors, the most important of which is the thick pneumococcal capsule that minimizes phagocytosis. Another virulence-associated trait is the tendency of this bacterium to undergo autolysis in stationary phase through activation of the cell wall-bound amidase LytA, which breaks down peptidoglycan. The exact function of autolysis in pneumococcal pathogenesis is, however, unclear. Here, we show the selective and specific inefficiency of wild-type S. pneumoniae for inducing production of phagocyte-activating cytokines in human peripheral blood mononuclear cells (PBMC). Indeed, clinical pneumococcal strains induced production of 30-fold less tumor necrosis factor (TNF), 15-fold less gamma interferon (IFN-gamma), and only negligible amounts of interleukin-12 (IL-12) compared with other closely related Streptococcus species, whereas the levels of induction of IL-6, IL-8, and IL-10 production were similar. If pneumococcal LytA was inactivated by mutation or by culture in a medium containing excess choline, the pneumococci induced production of significantly more TNF, IFN-gamma, and IL-12 in PBMC, whereas the production of IL-6, IL-8, and IL-10 was unaffected. Further, adding autolyzed pneumococci to intact bacteria inhibited production of TNF, IFN-gamma, and IL-12 in a dose-dependent manner but did not inhibit production of IL-6, IL-8, and IL-10 in response to the intact bacteria. Fragments from autolyzed bacteria inhibited phagocytosis of intact bacteria and reduced the in vitro elimination of pneumococci from human blood. Our results suggest that fragments generated by autolysis of bacteria with reduced viability interfere with phagocyte-mediated elimination of live pneumococci.
authors.affiliation: Department of Infectious Medicine/Clinical Bacteriology, Göteborg University, 413 46 Göteborg, Sweden. anna.martner@microbio.gu.se
authors.forename: Anna
authors.initials: A
authors.lastname: Martner
authors.forename: Susann
authors.initials: S
authors.lastname: Skovbjerg
authors.forename: James C
authors.initials: JC
authors.lastname: Paton
authors.forename: Agnes E
authors.initials: AE
authors.lastname: Wold
mesh_terms: D001426:Bacterial Proteins / Q000502:physiology; D001433:Bacteriolysis; D001770:Blood Bactericidal Activity; D016207:Cytokines / Q000096:biosynthesis*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D010586:Phagocytes / Q000276:immunology*; D010587:Phagocytosis; D013296:Streptococcus pneumoniae / Q000276:immunology*; D013301:Streptolysins / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D001426:Bacterial Proteins; D016207:Cytokines; D013301:Streptolysins; D014409:Tumor Necrosis Factor-alpha; C032290:plY protein, Streptococcus pneumoniae; D018664:Interleukin-12; D007371:Interferon-gamma