Influenza A Virus Triggers PANoptosis in Macrophages, Leading to Detrimental Inflammation

Strategic Insights -

A recent study published in Signal Transduction and Targeted Therapy has revealed that influenza A virus (IAV) induces PANoptosis, a form of lytic inflammatory cell death, in macrophages. The research, conducted by a team of scientists at the China-Japan Friendship Hospital, found that Ninjurin-1 (NINJ1), a mediator of plasma membrane rupture, plays a pivotal role in the immunopathology of IAV infection. The study also discovered an association between NINJ1 upregulation and poor outcomes in patients with COVID-19.

Key Takeaways:

  • Influenza A virus induces PANoptosis in macrophages, leading to detrimental inflammation.
  • Ninjurin-1 (NINJ1) mediates cell lysis and detrimental inflammation of PANoptosis during IAV infection.
  • IAV infection triggers an increase in the expression of NINJ1, which then oligomerizes and mediates cell lysis in infected macrophages.
  • The deficiency of NINJ1 prevents plasma membrane rupture and the release of DAMPs and IL-1b without affecting the progression of cell death.
  • Activation of any single PANoptosis pathway is sufficient to trigger the oligomerization of NINJ1 and robust cell lysis.
  • Ablation of NINJ1 in vivo alleviates IAV-induced lung injury and mortality.
  • The study reveals an association between NINJ1 upregulation and poor outcomes in patients with COVID-19.
  • NINJ1 is proposed as a bioindicator of disease severity and prognosis in viral pneumonia and viral sepsis.

Statistics:

  • The study is published in Signal Transduction and Targeted Therapy, a peer-reviewed journal.
  • The research was conducted by Yitian Xu, Ying Zheng, Yan Liu, and other authors at the China-Japan Friendship Hospital.
  • The study involved 10 authors, including Yitian Xu, Ying Zheng, Yan Liu, Cheng Wei, Juan Ren, Wenting Zuo, Runqing Gu, Hongyu Liu, Xiaoyan Deng, Yaxue Liu, Xiao Shang, Weiwei Ge, Ziyao Li, Yijiao Huang, Di He, Xuhui Shen, Zeyi Wang, Chen Lyu, Zai Wang, Yuxian Mu, and Zihuan Zhang.
  • The research received funding from the National Natural Science Foundation of China.
  • The study found an association between NINJ1 upregulation and poor outcomes in patients with COVID-19.

Sources:

  • Xu Y, Zheng Y, Liu Y, et al. Ninjurin-1 mediates cell lysis and detrimental inflammation of PANoptosis during influenza A virus infection. Signal Transduction and Targeted Therapy, 2025,10(1):1-13. (Signal Transduction and Targeted Therapy - http://www.nature.com/sigtrans/)
  • NewsRx. China-Japan Friendship Hospital Researchers Yield New Data on Influenza A Virus (Ninjurin-1 mediates cell lysis and detrimental inflammation of PANoptosis during influenza A virus infection). Virus Weekly. October 21, 2025; p 522.