| First Author | Gonzalez-Juarbe N | Year | 2020 |
| Journal | Cell Rep | Volume | 32 |
| Issue | 8 | Pages | 108062 |
| PubMed ID | 32846120 | Mgi Jnum | J:312124 |
| Mgi Id | MGI:6715901 | Doi | 10.1016/j.celrep.2020.108062 |
| Citation | Gonzalez-Juarbe N, et al. (2020) Influenza-Induced Oxidative Stress Sensitizes Lung Cells to Bacterial-Toxin-Mediated Necroptosis. Cell Rep 32(8):108062 |
| abstractText | 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. Pharmacoelogical 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. |
