| First Author | Garrison SP | Year | 2010 |
| Journal | PLoS Pathog | Volume | 6 |
| Issue | 12 | Pages | e1001240 |
| PubMed ID | 21203486 | Mgi Jnum | J:168334 |
| Mgi Id | MGI:4888059 | Doi | 10.1371/journal.ppat.1001240 |
| Citation | Garrison SP, et al. (2010) The p53-target gene puma drives neutrophil-mediated protection against lethal bacterial sepsis. PLoS Pathog 6(12):e1001240 |
| abstractText | Disruption of p53/Puma-mediated apoptosis protects against lethality due to DNA damage. Here we demonstrate the unexpected requirement of the pro-apoptotic p53-target gene Puma to mount a successful innate immune response to bacterial sepsis. Puma/ mice rapidly died when challenged with bacteria. While the immune response in Puma/ mice was unchanged in cell migration, phagocytosis and bacterial killing, sites of infection accumulated large abscesses and sepsis was progressive. Blocking p53/Puma-induced apoptosis during infection caused resistance to ROS-induced cell death in the CD49d+ neutrophil subpopulation, resulting in insufficient immune resolution. This study identifies a biological role for p53/Puma apoptosis in optimizing neutrophil lifespan so as to ensure the proper clearance of bacteria and exposes a counter-balance between the innate immune response to infection and survival from DNA damage. |
