PUBLICATION
Streptolysin S Inhibits Neutrophil Recruitment During the Early Stages of Streptococcus pyogenes Infection
- Authors
- Lin, A., Loughman, J.A., Zinselmeyer, B.H., Miller, M.J., and Caparon, M.G.
- ID
- ZDB-PUB-090819-18
- Date
- 2009
- Source
- Infection and Immunity 77(11): 5190-5201 (Journal)
- Registered Authors
- Caparon, Michael
- Keywords
- Streptococcus pyogenes, inflammation, zebrafish, polymorphonuclear leukocytes, 2 photon imaging
- MeSH Terms
-
- Animals
- Apoptosis/physiology
- Bacterial Proteins/genetics
- Bacterial Proteins/immunology
- Bacterial Proteins/metabolism
- Chemotaxis, Leukocyte/genetics
- Chemotaxis, Leukocyte/immunology
- Mice
- Neutrophil Infiltration/genetics
- Neutrophil Infiltration/immunology*
- Neutrophils/immunology
- Neutrophils/metabolism
- Reactive Oxygen Species/immunology
- Reactive Oxygen Species/metabolism
- Streptococcal Infections/genetics
- Streptococcal Infections/immunology*
- Streptococcal Infections/metabolism
- Streptococcus pyogenes
- Streptolysins/genetics
- Streptolysins/immunology
- Streptolysins/metabolism
- Zebrafish
- PubMed
- 19687200 Full text @ Infect. Immun.
Citation
Lin, A., Loughman, J.A., Zinselmeyer, B.H., Miller, M.J., and Caparon, M.G. (2009) Streptolysin S Inhibits Neutrophil Recruitment During the Early Stages of Streptococcus pyogenes Infection. Infection and Immunity. 77(11):5190-5201.
Abstract
In contrast to superficial tissues, Streptococcus pyogenes infection of deeper tissue can be associated with a significantly diminished inflammatory response, suggesting that this bacterium has the ability to both promote and to suppress inflammation. To examine this, we analyzed the behavior of an S. pyogenes mutant deficient in expression of the cytolytic toxin streptolysin S (SLS) using several models that evaluate events that occur during the first few hours of infection, including injection of zebrafish (adults, larvae and embryos), a transepithelial polymorphonuclear leukocyte (PMN) migration assay, and two-photon microscopy of mice in vivo. In contrast to wild type S. pyogenes, the SLS(-) mutant was associated with the robust recruitment of neutrophils and significantly reduced lethal myositis in adult zebrafish. Similarly, the mutant was attenuated in embryos in its ability to cause lethality. Infection of larvae muscle allowed an analysis of inflammation in real time, which revealed that the mutant now had recruitment of PMNs to the infection site. Analysis of transepithelial migration in vitro suggested that SLS inhibited host cells' production of signals chemotactic for neutrophils which contrasted with the pro-inflammatory effect of an unrelated cytolytic toxin, streptolysin O. Using two-photon microscopy of mice in vivo, we showed that the extravasation of neutrophils during infection with SLS(-) mutant bacteria was significantly accelerated compared to wild type S. pyogenes. Taken together, these data support a role for SLS in the inhibition of neutrophil recruitment during the early stages of S. pyogenes infection.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping