Influenza-Induced Oxidative Stress Sensitizes Lung Cells to Bacterial-Toxin-Mediated Necroptosis
| Autor: | Maryann P. Platt, Ashleigh N. Riegler, Ryan P. Gilley, Alexander S. Jureka, Norberto Gonzalez-Juarbe, Chad M. Petit, Jeffrey D. Brand, Carlos J. Orihuela, Kevin S. Harrod, John E. Trombley, Ninecia R. Scott, Peter H. Dube |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Programmed cell death Secondary infection Necroptosis Inflammation Lung injury medicine.disease_cause Article General Biochemistry Genetics and Molecular Biology Virus Microbiology Mice 03 medical and health sciences 0302 clinical medicine Influenza Human medicine Influenza A virus pneumonia influenza A virus Animals Humans lcsh:QH301-705.5 Lung business.industry Bacterial pneumonia respiratory system medicine.disease epithelial cells respiratory tract diseases Oxidative Stress Streptococcus pneumoniae cell death 030104 developmental biology lcsh:Biology (General) medicine.symptom business 030217 neurology & neurosurgery |
| Zdroj: | Cell reports Cell Reports, Vol 32, Iss 8, Pp 108062-(2020) |
| ISSN: | 2211-1247 |
| Popis: | SUMMARY Pneumonias caused by influenza A virus (IAV) co- and secondary bacterial infections are characterized by their severity and high mortality rate. Previously, we have shown that bacterial pore-forming toxin (PFT)-mediated necroptosis is a key driver of acute lung injury during bacterial pneumonia. Here, we evaluate the impact of IAV on PFT-induced acute lung injury during co- and secondary Streptococcus pneumoniae (Spn) infection. We observe that IAV synergistically sensitizes lung epithelial cells for PFT-mediated necroptosis in vitro and in murine models of Spn co-infection and secondary infection. Pharmacological induction of oxidative stress without virus sensitizes cells for PFT-mediated necroptosis. Antioxidant treatment or inhibition of necroptosis reduces disease severity during secondary bacterial infection. Our results advance our understanding on the molecular basis of co- and secondary bacterial infection to influenza and identify necroptosis inhibition and antioxidant therapy as potential intervention strategies. Graphical Abstract In Brief Gonzalez-Juarbe et al. identify necroptosis as a pathway modulating disease severity during secondary bacterial infection (SBI) following influenza virus infection. They show that influenza-virus-induced oxidative stress is required to sensitize pulmonary cells to the pro-necroptotic activity of bacterial pore-forming toxins, providing a mechanism to explain the necrosis observed during SBI. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|