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Streptococcus pyogenes M49 plasminogen/plasmin binding facilitates keratinocyte invasion via integrin-integrin-linked kinase (ILK) pathways and protects from macrophage killing

Authors :
Nadja Patenge
Nikolai Siemens
Bernd Kreikemeyer
Tomas Fiedler
Juliane Otto
Source :
The Journal of biological chemistry. 286(24)
Publication Year :
2011

Abstract

The entry into epithelial cells and the prevention of primary immune responses are a prerequisite for a successful colonization and subsequent infection of the human host by Streptococcus pyogenes (group A streptococci, GAS). Here, we demonstrate that interaction of GAS with plasminogen promotes an integrin-mediated internalization of the bacteria into keratinocytes, which is independent from the serine protease activity of potentially generated plasmin. α(1)β(1)- and α(5)β(1)-integrins were identified as the major keratinocyte receptors involved in this process. Inhibition of integrin-linked kinase (ILK) expression by siRNA silencing or blocking of PI3K and Akt with specific inhibitors, reduced the GAS M49-plasminogen/plasmin-mediated invasion of keratinocytes. In addition, blocking of actin polymerization significantly reduced GAS internalization into keratinocytes. Altogether, these results provide a first model of plasminogen-mediated GAS invasion into keratinocytes. Furthermore, we demonstrate that plasminogen binding protects the bacteria against macrophage killing.

Details

ISSN :
1083351X
Volume :
286
Issue :
24
Database :
OpenAIRE
Journal :
The Journal of biological chemistry
Accession number :
edsair.doi.dedup.....95dd0572fa081dcf04a96a6eecbb8fc6