Journal Article

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

Hu, Yunhao, Liu, Bin, Zhang, Wenlong, Wang, Junwei, Yang, Meimei

2025

Overview

Trueperella pyogenes ( T. pyogenes ) is an important opportunistic pathogen in animals and can also cause diseases in humans. Previous studies have shown that T. pyogenes 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 T. pyogenes cells (iTP) and pyolysin (PLO, a major virulence factor of T. pyogenes ) can promote the transcription of the IL-1β gene both in vivo and in vitro . 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 T. pyogenes 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 T. pyogenes and the interactions between T. pyogenes and host immune system.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Actinomycetaceae - immunology / Actinomycetales Infections - immunology / Actinomycetales Infections - metabolism / Actinomycetales Infections - microbiology / Animals / Biofilms / Bone marrow / Caspase 1 - metabolism / Caspase-1 / Hemolysin Proteins - metabolism / IL-1β / Immune system / Immunology / Inflammatory diseases / Interleukin 1 / Interleukin-1beta - biosynthesis / Interleukin-1beta - genetics / Interleukin-1beta - immunology / Interleukin-1beta - metabolism / Laboratory animals / Macrophages / Macrophages - immunology / Macrophages - metabolism / Macrophages - microbiology / Membranes / Mice / Mice, Inbred C57BL / NF-kappa B - metabolism / NF-κB / NF-κB protein / NLR Family, Pyrin Domain-Containing 3 Protein - metabolism / NLRP3 / Opportunist infection / Pathogenesis / Pets / Plasmids / PLO / Post-translation / Potassium - metabolism / Proteins / Pyolysin / T. pyogenes / Toxins / Transcription / Trueperella pyogenes / Virulence / Virulence factors