Staphylococcus epidermidis-Derived Protease Esp Mediates Proteolytic Activation of Pro.IL-1β in Human Keratinocytes

The Gram-positive bacterium Staphylococcus epidermidis (SE) is an abundant skin commensal. It plays an important role in cutaneous defense by activation of IL-1 signaling. In keratinocytes (KCs), SE induces the release of mature IL-beta. IL-beta serves as an important cytokine of host defense. It contains an N-terminal pro-domain that has to be cleaved off to generate active mature IL-beta. Typically, the processing and release of IL-beta are associated with inflammasome assembly and activation of the protease caspase-1. In this study, we report that the bacterial challenge of KCs with SE induced the release of mature IL-beta in a caspase-1-independent manner. Instead, the SE-derived serine protease Esp was identified as a pro-IL-beta -processing factor leading to a proteolytic maturation of active IL-beta. Esp production and secretion by various SE strains correlated with their capacity to induce the release of mature IL-beta in human primary KCs. Reconstitution of Esp-lacking SE strains with Esp enhanced their capacity to induce IL-beta release in KCs and skin. Intracellular abundance of pro-IL-beta and cytotoxic effects of SE suggest a release of pro-IL-beta during injury, followed by extracellular Esp-mediated processing to mature IL-beta. These findings provide further insights into how a skin commensal interacts with KCs to activate cutaneous host innate defense.

Automated summary

Staphylococcus epidermidis (SE) plays an important role in skin defense by activating IL-1 signaling. A serine protease called Esp produced by SE was found to be crucial in the release of mature IL-beta in a caspase-1-independent manner.