This study describes the target receptor and mechanism of action of Staphylococcal superantigen like 13 (SSL13), a secret protein reside on S.aureus immune evasion cluster 2(IEC-2) that previously supposed to modulate immune evasion. In sharp contrast to the characterized SSLs located on the staphylococcal pathogenicity island 2 (SPI-2) , that inhibit immune functions, We demonstrate SSL13 is a chemoattractant and a neutrophil activator that acts via the FPR2. Therefore, SSL13 is a unique SSL member not belonging to the immune evasion class, but is a pathogen alarming molecule sensed by the FPR2. Our study provides a new conception of SSLs, that not only inhibit host immune processes but also recruit human neutrophils to the site of infection, where S. aureus can be disarmed by secreted immune evasion proteins and used as vesicles to other parts of the host. This allow us to better understand of S. aureus pathological processes.

Staphylococcal Superantigen-Like (SSL) proteins, one of major virulence factor families produced by Staphylococcus aureus, were previously demonstrated to be immune evasion molecules that interfere with a variety of innate immune defenses, e.g. SSL5, SSL7, and SSL10. However, in contrast to these characterized SSLs, that inhibit immune functions, we show that SSL13 is a strong activator of neutrophils via the formyl-peptide receptor 2 (FPR2). Moreover, our data showed SSL13 acts as a chemoattractant, induces degranulation and oxidative burst in neutrophils. As with many other staphylococcal immune evasion proteins, SSL13 shows a high degree of human specificity. SSL13 is not able to efficiently activate mouse neutrophils, hampering in vivo experiments. In conclusion, SSL13 is a neutrophil chemoattractant and activator that acts via the FPR2. Therefore, SSL13 is a unique SSL member that does not belong to the immune evasion class, but is a pathogen alarming molecule.