The ScpC protease of Streptococcus pyogenes affects the outcome of sepsis in a murine model.

Abstract:

: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.

journal_name

Infect Immun

journal_title

Infection and immunity

authors

Sjölinder H,Lövkvist L,Plant L,Eriksson J,Aro H,Jones A,Jonsson AB

doi

10.1128/IAI.00128-08

subject

Has Abstract

pub_date

2008-09-01 00:00:00

pages

3959-66

issue

9

eissn

0019-9567

issn

1098-5522

pii

IAI.00128-08

journal_volume

76

pub_type

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