Pasteurella multocida toxin induces apoptosis of respiratory epithelial cells by activating the PERK-NF-κB-DR5 signaling axis

  • Vet Microbiol. 2026 Apr:315:110921. doi: 10.1016/j.vetmic.2026.110921.
Fei Wang  1 ,  Yuhao Lei  1 ,  Menghan Chen  1 ,  Haixin Bi  1 ,  Yayuan Luo  1 ,  Fangfang Bai  1 ,  Lin Hua  1 ,  Huanchun Chen  1 ,  Qigai He  2 ,  Bin Wu  3 ,  Zhong Peng  4
Affiliations
  • 1. National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; Hubei Hongshan Laboratory, Wuhan 430070, China; Frontiers Center for Animal Breeding and Sustainable Production, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China.
  • 2. National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; Hubei Hongshan Laboratory, Wuhan 430070, China; Frontiers Center for Animal Breeding and Sustainable Production, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China. Electronic address: [email protected].
  • 3. National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; Hubei Hongshan Laboratory, Wuhan 430070, China; Frontiers Center for Animal Breeding and Sustainable Production, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China; National Center of Technology Innovation for Pigs, Chongqing 402460, China. Electronic address: [email protected].
  • 4. National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; Hubei Hongshan Laboratory, Wuhan 430070, China; Frontiers Center for Animal Breeding and Sustainable Production, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China; National Center of Technology Innovation for Pigs, Chongqing 402460, China. Electronic address: [email protected].
PMID: 41637966 DOI: 10.1016/j.vetmic.2026.110921
Abstract

Pasteurella multocida toxin (PMT) is a key virulence factor produced by some strains of the zoonotic respiratory pathogen Pasteurella multocida (P. multocida). The role of PMT in inducing damage and Apoptosis in respiratory epithelial cells remains unclear. In this study, we investigated the molecular mechanism through which PMT induces Apoptosis in porcine tracheal epithelial cells (NPTr). It was found that high concentrations of PMT specifically induced caspase-3-dependent Apoptosis, an effect absent in its mutant form. Mechanistic analysis demonstrated that PMT activated the NF-κB signaling pathway via the PERK pathway associated with Endoplasmic Reticulum (ER) stress, significantly upregulating the expression of the Death Receptor 5 (DR5) which subsequently activated Caspase-3, triggering Apoptosis. Crucial validation experiments showed that knocking out the DR5-encoding gene TNFRSF10B nearly completely inhibited PMT-induced Apoptosis and significantly restored cell viability. In summary, this study identifies the PERK-NF-κB-DR5 signaling axis as the principal regulatory pathway for PMT-induced Apoptosis in porcine tracheal epithelial cells.

Keywords
Apoptosis; Death receptor 5; NF-κB pathway; PERK pathway; Pasteurella multocida toxin.
Products