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

Abstract

<i>Trueperella pyogenes</i> (<i>T. pyogenes</i>) 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 <i>T. pyogenes</i> to induce pyroptosis was first determined. Then, pyolysin (PLO), a cholesterol-dependent cytolysin secreted by <i>T. pyogenes</i>, was found to be closely related to <i>T. pyogenes</i>-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 <i>T. pyogenes</i> and PLO-induced IL-1β release. Taken together, these results indicate <i>T. pyogenes</i>-induced inflammation is related to PLO-induced pyroptosis and IL-1β release. Our work shed light on the pathogenesis of <i>T. pyogenes</i> and the interaction between <i>T. pyogenes</i> and hosts' immune system.