Inflammatogenic properties of bacterial DNA following cutaneous exposure

Abstract

Bacterial DNA and oligodeoxynucleotides containing cytosine-phosphate-guanosine sequences and thereby mimicking prokaryotic DNA, have recently been shown to exert potent immunostimulatory properties. As skin normally harbors bacteria, and as the bacterial content and the levels of bacterial degradation products increase during skin infection, we analyzed the potential inflammatogenic role of bacterial DNA and oligodeoxynucleotides in a mouse model of cutaneous inflammation. Bacterial DNA from Staphylococcus aureus was injected intradermally into mice and its inflammatogenic properties were compared with synthetic phosphodiester and phosphorothioate cytosine-phosphate-guanosine- or GpC-containing oligodeoxynucleotides. A peak inflammatory infiltrate in the skin was seen already 2 d after injection with either bacterial DNA or the phosphodiester cytosine-phosphate-guanosine-oligodeoxynucleotides. In contrast, nuclease-resistant phosphorothioate cytosine-phosphate-guanosine-induced dermatitis peaked 7 d after intradermal injection. The inflammatory infiltrates consisted mainly of macrophages, and depletion of this cell population resulted in a significant (p=0.0001) decrease in the severity of inflammation, which suggests that macrophages play a central part in inflammatory responses in the skin following exposure to cytosine-phosphate-guanosine-containing oligodeoxynucleotides. A significant decrease in local inflammatory infiltrate was also seen in mice with deficiencies in neutrophil or lymphocyte populations, which indicates that these cell populations may also be involved in mediating inflammatory signals after the injection of immunostimulatory DNA sequences. In summary, our results suggest that bacterial DNA is an important virulence determinant and inflammatory stimulus during skin infections.