Sirtuin1 Targeting Reverses Innate and Adaptive Immune Tolerance in Septic Mice.

ABSTRACT: Resistance and tolerance to infection are two universal fitness and survival strategies used by inflammation and immunity in organisms and cells to guard homeostasis. During sepsis, however, both strategies fail, and animal and human victims often die from combined innate and adaptive immune suppression with persistent bacterial and viral infections. NAD⁺-sensing nuclear sirtuin1 (SIRT1) epigenetically guards immune and metabolic homeostasis during sepsis. Pharmacologically inhibiting SIRT1 deacetylase activity in septic mice reverses monocyte immune tolerance, clears infection, rebalances glycolysis and glucose oxidation, resolves organ dysfunction, and prevents most septic deaths. Whether SIRT1 inhibition during sepsis treatment concomitantly reverses innate and T cell antigen

SUBMITTER: Martin AN 

PROVIDER: S-EPMC6057336 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature