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-kappaB. Furthermore, pharmacological inhibition of
NF-kappaB, decreased MIG synthesis in IFN-gamma activated cells, demonstrating a key role for
NF-kappaB 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 an 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 M1
protein and intact S. pyogenes, thereby modulating an antibacterial innate host response that may have bearing on the outcome of streptococcal
pharyngitis.