M1 protein of Streptococcus pyogenes increases production of the antibacterial CXC chemokine MIG/CXCL9 in pharyngeal epithelial cells
Författare
Summary, in English
Streptococcus pyogenes adheres to epithelial cells of the human pharynx where it can cause pharyngitis. To counteract infection. inflamed epithelium produces peptide antibiotics, among them the CXC chemokine MIG/CXCL9. M protein is both a surface-associated and released virulence factor of S. pyogenes. Here we show that soluble M1 protein enhances MIG gene expression and synthesis in IFN-gamma stimulated epithelial cells. M1 protein was recognized both by resting and IFN-gamma activated pharyngeal epithelial cells as detected by activation of the transcription factor NF-kappa B. Furthermore, pharmacological inhibition of NF-kappa B. decreased MIG synthesis in IFN-gamma activated cells, demonstrating a key role for NF-kappa B in mediating the enhanced response. Microarrays were used to investigate expression of recognized antimicrobial peptides in pharyngeal epithelial cells after stimulation with a combination of IFN-gamma and M1 protein. Amongst the most up-regulated and expressed genes, were several antibacterial CC and CXC chemokines. To investigate all in vivo context, pharyngeal mucosa was stimulated in vitro and MIG could be detected by immunohistochemistry in epithelial cells. The results show that epithelial cells can recognize solubilized M I protein and intact S. pyogenes, thereby modulating an antibacterial innate host response that may have bearing oil the outcome of streptococcal pharyngitis.
Avdelning/ar
Publiceringsår
2007
Språk
Engelska
Sidor
224-233
Publikation/Tidskrift/Serie
Microbial Pathogenesis
Volym
43
Issue
5-6
Dokumenttyp
Artikel i tidskrift
Förlag
Academic Press
Ämne
- Infectious Medicine
Nyckelord
- innate immunity
- mucosa
- infection
Status
Published
Forskningsgrupp
- Infection and immunomodulation
ISBN/ISSN/Övrigt
- ISSN: 1096-1208