Myeloid cell sirtuin-1 expression does not alter host immune responses to gram-negative endotoxemia or gram-positive bacterial infection

Laura E. Crotty Alexander, Brenda J. Marsh, Anjuli M. Timmer, Ann E. Lin, Kayvan Zainabadi, Agnieszka Czopik, Leonard Guarente, Victor Nizet

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

The role of sirtuin-1 (SIRT1) in innate immunity, and in particular the influence of SIRT1 on antimicrobial defense against infection, has yet to be reported but is important to define since SIRT1 inhibitors are being investigated as therapeutic agents in the treatment of cancer, Huntington's disease, and autoimmune diseases. Given the therapeutic potential of SIRT1 suppression, we sought to characterize the role of SIRT1 in host defense. Utilizing both pharmacologic methods and a genetic knockout, we demonstrate that SIRT1 expression has little influence on macrophage and neutrophil antimicrobial functions. Myeloid SIRT1 expression does not change mortality in gramnegative toxin-induced shock or gram-positive bacteremia, suggesting that therapeutic suppression of SIRT1 may be done safely without suppression of myeloid cell-specific immune responses to severe bacterial infections.

Original languageEnglish (US)
Article number0084481
JournalPloS one
Volume8
Issue number12
DOIs
StatePublished - Dec 26 2013
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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