Pyolysin of Induces Pyroptosis and IL-1β Release in Murine Macrophages Through Potassium/NLRP3/Caspase-1/Gasdermin D Pathway.

() is a commensal and an opportunistic pathogen of animals. This organism can cause inflammatory diseases, such as pneumonia, mastitis and endometritis in hosts. However, the molecular basis for the pro-inflammatory properties of this organism is still largely unknown. In the current study, using murine macrophages as model, the ability of to induce pyroptosis was first determined. Then, pyolysin (PLO), a cholesterol-dependent cytolysin secreted by , was found to be closely related to -induced pyroptosis. Next, our work showed that PLO can form pores in the cell membrane, leading to the efflux of potassium (K), NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediated caspase-1 activation, and gasdermin D (GSDMD) cleavage. Inhibition of the K/NLRP3/caspase-1/GSDMD pathway abolished and PLO-induced IL-1β release. Taken together, these results indicate -induced inflammation is related to PLO-induced pyroptosis and IL-1β release. Our work shed light on the pathogenesis of and the interaction between and hosts' immune system.