Host-bacterium relationship in staphylococcal skin infection

Abstract: Skin infections caused by Staphylococcus aureus are commonly occuring, both in the community and in hospitals. Despite the high prevalence of this condition, little is known about the host immune responsiveness and bacterial virulence factors during S. aureus skin infection. To enable an in-depth understanding of the host-bacterium relationship, we assessed a murine model of cutaneous infection. Mice inoculated intradermally with high numbers of staphylococci (108 CFU) displayed clinical and histopathological signs of local inflammation, but lacked signs of sepsis. In this model, the role of a superantigen, TSST-1, was assessed using isogenic S. aureus strains. Mice inoculated with the TSST-1-producing strain showed a weight decrease and a preferential influx of CD4+T lymphocytes to the skin.To assess the role of neutrophils in staphylococcal skin infection, mice were given granulocyte-depleting monoclonal antibody prior to intracutaneous inoculation with staphylococci, resulting in substantial early neutropenia. The granulocyte-depleted mice displayed a more severe clinical infection, a higher bacterial burden in the blood and in the skin, generalized signs of inflammation and a weight loss. Early recruitment of neutrophils and possibly phagocytosis in the initial stages of S. aureus infection was concluded to be critical for the outcome of staphylococcal skin infection.The high number of gamma/delta-expressing T cells found in the epithelial lining layer suggests that they form a first line of defense against invading pathogens. To evaluate the role of gamma/delta T cell receptor(TCR)-expressing lymphocytes in cutaneous infection caused by S. aureus, mice lacking gamma/delta TCR-expressing cells were inoculated intradermally with S. aureus and compared with S. aureus-infected congenic control mice. We observed early and transient deficiency in the bacterial elimination in gamma/delta T cell deficient mice, which supports the notion that cutaneous gamma/delta T cells act as an early barrier to prevent staphylococcal infections of the skin.Bacterial DNA and synthetic oligodeoxynucleotides (ODNs) containing CpG sequences, mimicking prokaryotic DNA, have recently been shown to exert potent immunostimulatory properties. Bacterial DNA from S. aureus and CpG-containing ODNs were injected intradermally, giving rise to an inflammatory infiltrate. Depletion of monocytes/macrophages resulted in a significant decrease in the severity of inflammation, which suggests that macrophages play a central role in inflammatory responses in the skin following exposure to bacterial DNA. In summary, our results suggest that bacterial DNA is an important virulence determinant and inflammatory stimulus during skin infections.In this model of cutaneous staphylococcal infection, we have assessed the role of some bacterial virulence factors, such as bacterial DNA and TSST-1, and the importance of some host immune cells, such as neutrophils and gamma/delta T cells, showing crucial host-bacterium relationship in the development of inflammatory skin lesions.