Rapid pathogen-specific recruitment of immune effector cells in the skin by secreted toxins

Swift recruitment of phagocytic leucocytes is critical in preventing infection when bacteria breach through the protective layers of the skin. According to canonical models, this occurs via an indirect process that is initiated by contact of bacteria with resident skin cells and which is independent of the pathogenic potential of the invader. Here we describe a more rapid mechanism of leucocyte recruitment to the site of intrusion of the important skin pathogen Staphylococcus aureus that is based on direct recognition of specific bacterial toxins, the phenol-soluble modulins (PSMs), by circulating leucocytes. We used a combination of intravital imaging, ear infection and skin abscess models, and in vitro gene expression studies to demonstrate that this early recruitment was dependent on the transcription factor EGR1 and contributed to the prevention of infection. Our findings refine the classical notion of the non-specific and resident cell-dependent character of the innate immune response to bacterial infection by demonstrating a pathogen-specific high-alert mechanism involving direct recruitment of immune effector cells by secreted bacterial products. Staphylococcus aureus phenol-soluble modulin toxins trigger a fast immune response that involves recruitment of leucocytes to the site of infection via the transcription factor EGR1.

Automated summary

Research has revealed that toxins from the skin pathogen Staphylococcus aureus, known as PSMs, can trigger a rapid immune response by directly recognizing and activating the transcription factor EGR1, leading to the recruitment of leucocytes to the site of infection and thus preventing infection.