Abstract
Trueperella pyogenes (T. pyogenes) 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 T. pyogenes to induce pyroptosis was first determined. Then, pyolysin (PLO), a cholesterol-dependent cytolysin secreted by T. pyogenes, was found to be closely related to T. pyogenes-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 T. pyogenes and PLO-induced IL-1β release. Taken together, these results indicate T. pyogenes-induced inflammation is related to PLO-induced pyroptosis and IL-1β release. Our work shed light on the pathogenesis of T. pyogenes and the interaction between T. pyogenes and hosts’ immune system.
Highlights
Trueperella pyogenes (T. pyogenes) is a commensal and an opportunistic pathogen of many animal species [1]
We found that the gasdermin D (GSDMD) cleavage induced by 10 multiplicity of infection (MOI) T. pyogenes was completely abolished by cholesterol (200 mM) (Figure 2B), suggesting that the bacterial component(s) responsible for T. pyogenes induced pyroptosis is/are sensitive to cholesterol
Since caspase-1 activation is closely related to NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome [22], the current study focused on the activation mechanisms of the NLRP3 inflammasome
Summary
Trueperella pyogenes (T. pyogenes) is a commensal and an opportunistic pathogen of many animal species [1]. This organism can cause purulent infections in animals when the host’s immune system is compromised by unfavorable factors, such as heat, wound, transportation, and primary infections [2]. Cases of human T. pyogenes infection have been reported [3–5]. Inflammatory diseases, such as pneumonia, mastitis, endometritis, and soft tissue and organ abscesses, are the main manifestation of T. pyogenes infection in animals [1]. The molecular basis for the pro-inflammatory properties of this organism is still largely unknown
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