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Infection and Immunity, September 2008, p. 3959-3966, Vol. 76, No. 9
0019-9567/08/$08.00+0     doi:10.1128/IAI.00128-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

The ScpC Protease of Streptococcus pyogenes Affects the Outcome of Sepsis in a Murine Model

Hong Sjölinder,^1, Lena Lövkvist,^1, Laura Plant,² Jens Eriksson,¹ Helena Aro,¹ Allison Jones,¹ and Ann-Beth Jonsson^1*

Department of Medical Biochemistry and Microbiology, Biomedical Centre, Uppsala University, 751 23 Uppsala, Sweden,¹ Department of Microbiology, Tumorbiology and Cellbiology, Karolinska Institutet, 171 77 Solna, Sweden²

Received 30 January 2008/ Returned for modification 7 April 2008/ Accepted 6 June 2008

The ScpC protease of Streptococcus pyogenes degrades interleukin-8 (IL-8), a chemokine that mediates neutrophil transmigration and activation. The ability to degrade IL-8 differs dramatically among clinical isolates of S. pyogenes. Bacteria expressing ScpC overcome immune clearance by preventing the recruitment of neutrophils in soft tissue infection of mice. To study the role of ScpC in streptococcal sepsis, we generated an ScpC mutant that did not degrade IL-8 and thus failed to prevent the recruitment of immune cells as well as to cause disease after soft tissue infection. In a murine model of sepsis, challenge with the ScpC mutant resulted in more severe systemic disease with higher bacteremia levels and mortality than did challenge with the wild-type strain. As expected, the blood level of KC, the murine IL-8 homologue, increased in mice infected with the ScpC mutant. However, the elevated KC levels did not influence neutrophil numbers in blood, as it did in soft tissue, indicating that additional factors contributed to neutrophil transmigration in blood. In addition, the absence of ScpC increased tumor necrosis factor, IL-6, and C5a levels in blood, which contributed to disease severity. Thus, the ScpC mutant triggers high neutrophil infiltration but not lethal outcome after soft tissue infection, whereas intravenous infection leads to highly aggressive systemic disease.

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* Corresponding author. Mailing address: Department of Medical Biochemistry and Microbiology, Uppsala University, SE 75123 Uppsala, Sweden. Phone: 46-(0)18-4714507. Fax: 46-(0)18-4714673. E-mail: Ann-Beth.Jonsson{at}imbim.uu.se

Published ahead of print on 23 June 2008.

Editor: J. N. Weiser

H.S. and L.L. contributed equally.

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Infection and Immunity, September 2008, p. 3959-3966, Vol. 76, No. 9
0019-9567/08/$08.00+0     doi:10.1128/IAI.00128-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

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