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

ABSTRACT: 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 clearanc

SUBMITTER: Garrison SP 

PROVIDER: S-EPMC3009602 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature