The p53-target gene puma drives neutrophil-mediated protection against lethal bacterial sepsis

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. puma2/2 mice rapidly died when challenged with bacteria. while the immune response in puma2/2 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. © 2010 garrison et al.