Trueperella pyogenes promotes the synthesis and maturation of IL-1β in murine macrophages

<i>Trueperella pyogenes</i> (<i>T. pyogenes</i>) is an important opportunistic pathogen in animals and can also cause diseases in humans. Previous studies have shown that <i>T. pyogenes</i> infection can upregulate the levels of pro-inflammatory cytokines, such as interleukin-1 beta (IL-1β), in host tissues. However, the underlying mechanisms are not yet fully understood. In the current study, we found that both inactivated <i>T. pyogenes</i> cells (iTP) and pyolysin (PLO, a major virulence factor of <i>T. pyogenes</i>) can promote the transcription of the IL-1β gene both <i>in vivo</i> and <i>in vitro</i>. iTP-caused upregulation of IL-1β gene transcription is dependent on nuclear factor-kappa B (NF-κB). On the other hand, we determined that PLO, but not iTP, can promote the maturation of IL-1β by activating caspase-1-mediated processing of pro-IL-1β. Further, we confirmed that PLO can induce potassium ion (K⁺) efflux in mouse macrophages, thereby activating caspase-1 in a Nod-like receptor protein 3 (NLRP3)-dependent manner. Blocking K⁺ efflux or knocking down the expression of NLRP3 both inhibited caspase-1 activation and pro-IL-1β processing. Taken together, these findings demonstrate that <i>T. pyogenes</i> can promote IL-1β expression at both the transcriptional and post-translational levels in a murine macrophage model. These results significantly enhance our understanding of the pathogenesis of <i>T. pyogenes</i> and the interactions between <i>T. pyogenes</i> and host immune system.