The p53-Target Gene Drives Neutrophil-Mediated Protection against Lethal Bacterial Sepsis

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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.

Vyšlo v časopise: The p53-Target Gene Drives Neutrophil-Mediated Protection against Lethal Bacterial Sepsis. PLoS Pathog 6(12): e32767. doi:10.1371/journal.ppat.1001240
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1001240

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