This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Google Scholar
Right arrow Articles by Martner, A.
Right arrow Articles by Wold, A. E.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Martner, A.
Right arrow Articles by Wold, A. E.

 Previous Article  |  Next Article 

Infection and Immunity, September 2009, p. 3826-3837, Vol. 77, No. 9
0019-9567/09/$08.00+0     doi:10.1128/IAI.00290-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Streptococcus pneumoniae Autolysis Prevents Phagocytosis and Production of Phagocyte-Activating Cytokines{triangledown} ,{dagger}

Anna Martner,1* Susann Skovbjerg,1 James C. Paton,2 and Agnes E. Wold1

Department of Infectious Medicine/Clinical Bacteriology, Göteborg University, Guldhedsgatan 10A, 413 46 Göteborg, Sweden,1 Research Centre for Infectious Diseases, School of Molecular and Biomedical Science, University of Adelaide, S.A. 5005, Australia2

Received 12 March 2009/ Returned for modification 15 May 2009/ Accepted 9 June 2009

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.

* Corresponding author. Mailing address: Department of Infectious Medicine/Clinical Bacteriology, Göteborg University, Guldhedsgatan 10 A, 413 46 Göteborg, Sweden. Phone: 46 31 342 4623. Fax: 46 31 342 4975. E-mail: anna.martner{at}microbio.gu.se

{triangledown} Published ahead of print on 15 June 2009.

{dagger} Supplemental material for this article may be found at http://iai.asm.org/.

Editor: J. N. Weiser

Infection and Immunity, September 2009, p. 3826-3837, Vol. 77, No. 9
0019-9567/09/$08.00+0     doi:10.1128/IAI.00290-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»