Scholarlink

<p>Effective host defense requires coordinated regulation of immune activation, metabolism, and redox balance, yet how these processes are integrated remains unclear. Here, we identify dipeptidyl peptidase 3 (Dpp3) as a regulator of immune activation thresholds during bacterial infection. <i>Dpp3−/−</i> mice display enhanced resistance to <i>Klebsiella pneumoniae</i>, with early divergence in bacterial burden, improved survival, preserved tissue architecture, and reduced systemic inflammation. Adoptive transfer experiments demonstrate that Dpp3-deficient immune cells are sufficient to confer protection, indicating a cell-intrinsic effect. Mechanistically, Dpp3 deficiency impairs inducible Nrf2 stabilization, resulting in amplified ROS accumulation and enhanced NF-κB–associated responses. Integrated metabolomic, bioenergetic, and proteomic analyses reveal coordinated mitochondrial remodeling and activation of inflammatory signaling networks, consistent with a metabolically primed immune state. Collectively, these findings establish Dpp3 as a systems-level regulator integrating redox control and immunometabolism to calibrate antimicrobial responses during infection.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Dipeptidyl peptidase 3 sets the threshold for immune activation and survival during experimental bacterial infection

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月6日

查看全文
  • Amanda Facoetti,
  • Luca Lambroia,
  • Elena Fontana,
  • Federico Nicchiotti,
  • Maria Lucia Schiavone,
  • Dario Strina,
  • Raffaello Viganò,
  • Francesca Brambilla,
  • Davide Mangioni,
  • Samantha Scaramuzza,
  • Sara Mallia,
  • Marcella Bonanomi,
  • Andrea Farini,
  • Mirella Meregalli,
  • Debora Mostosi,
  • Giuseppe Rocca,
  • Ciro Menale,
  • Cecilia Garlanda,
  • Antonio Muscatello,
  • Alessandra Bandera,
  • Daniela Gaglio,
  • Cristina Sobacchi,
  • Yvan Torrente,
  • Pierluigi Mauri,
  • Dario Di Silvestre,
  • Clelia Peano,
  • Francesca Granucci,
  • Veronica Marrella,
  • Barbara Cassani

摘要

Effective host defense requires coordinated regulation of immune activation, metabolism, and redox balance, yet how these processes are integrated remains unclear. Here, we identify dipeptidyl peptidase 3 (Dpp3) as a regulator of immune activation thresholds during bacterial infection. Dpp3−/− mice display enhanced resistance to Klebsiella pneumoniae, with early divergence in bacterial burden, improved survival, preserved tissue architecture, and reduced systemic inflammation. Adoptive transfer experiments demonstrate that Dpp3-deficient immune cells are sufficient to confer protection, indicating a cell-intrinsic effect. Mechanistically, Dpp3 deficiency impairs inducible Nrf2 stabilization, resulting in amplified ROS accumulation and enhanced NF-κB–associated responses. Integrated metabolomic, bioenergetic, and proteomic analyses reveal coordinated mitochondrial remodeling and activation of inflammatory signaling networks, consistent with a metabolically primed immune state. Collectively, these findings establish Dpp3 as a systems-level regulator integrating redox control and immunometabolism to calibrate antimicrobial responses during infection.