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

Area of Science:

• Immunology
• Microbiology
• Pathogenesis

Background:

• Trueperella pyogenes is an opportunistic pathogen causing animal and human diseases.
• T. pyogenes infection elevates pro-inflammatory cytokines like IL-1β.
• Mechanisms underlying IL-1β upregulation by T. pyogenes are not fully understood.

Purpose of the Study:

• Investigate the molecular mechanisms of IL-1β regulation by T. pyogenes.
• Determine the roles of inactivated T. pyogenes (iTP) and pyolysin (PLO) in IL-1β expression.
• Elucidate the pathways involved in IL-1β transcriptional and post-translational control.

Main Methods:

• In vivo and in vitro experiments using inactivated T. pyogenes (iTP) and pyolysin (PLO).
• Analysis of IL-1β gene transcription, NF-κB activation, and caspase-1 mediated processing.
• Assessment of potassium ion (K+) efflux, NLRP3 inflammasome activation, and caspase-1 activity in murine macrophages.

Main Results:

• Both iTP and PLO upregulated IL-1β gene transcription.
• iTP-induced IL-1β transcription was NF-κB dependent.
• PLO, but not iTP, promoted IL-1β maturation via caspase-1 activation.
• PLO induced K+ efflux, activating caspase-1 in an NLRP3-dependent manner, leading to pro-IL-1β processing.

Conclusions:

• T. pyogenes enhances IL-1β expression at both transcriptional and post-translational levels.
• NF-κB mediates iTP-induced IL-1β transcription.
• PLO-induced IL-1β maturation involves K+ efflux, NLRP3 inflammasome, and caspase-1 activation.
• Findings deepen understanding of T. pyogenes pathogenesis and host immune interactions.