AUTHOR=Liang Hongmin , Wang Bing , Wang Junwei , Ma Bo , Zhang Wenlong 

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

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.832458

DOI=10.3389/fimmu.2022.832458

ISSN=1664-3224

ABSTRACT=<p><italic>Trueperella pyogenes</italic> (<italic>T. pyogenes</italic>) 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 <italic>T. pyogenes</italic> to induce pyroptosis was first determined. Then, pyolysin (PLO), a cholesterol-dependent cytolysin secreted by <italic>T. pyogenes</italic>, was found to be closely related to <italic>T. pyogenes</italic>-induced pyroptosis. Next, our work showed that PLO can form pores in the cell membrane, leading to the efflux of potassium (K<sup>+</sup>), NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediated caspase-1 activation, and gasdermin D (GSDMD) cleavage. Inhibition of the K<sup>+</sup>/NLRP3/caspase-1/GSDMD pathway abolished <italic>T. pyogenes</italic> and PLO-induced IL-1β release. Taken together, these results indicate <italic>T. pyogenes</italic>-induced inflammation is related to PLO-induced pyroptosis and IL-1β release. Our work shed light on the pathogenesis of <italic>T. pyogenes</italic> and the interaction between <italic>T. pyogenes</italic> and hosts’ immune system.</p>