TY - JOUR
T1 - Myeloid cell sirtuin-1 expression does not alter host immune responses to gram-negative endotoxemia or gram-positive bacterial infection
AU - Crotty Alexander, Laura E.
AU - Marsh, Brenda J.
AU - Timmer, Anjuli M.
AU - Lin, Ann E.
AU - Zainabadi, Kayvan
AU - Czopik, Agnieszka
AU - Guarente, Leonard
AU - Nizet, Victor
PY - 2013/12/26
Y1 - 2013/12/26
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0084481
DO - 10.1371/journal.pone.0084481
M3 - Article
C2 - 24386389
AN - SCOPUS:84891327061
SN - 1932-6203
VL - 8
JO - PloS one
JF - PloS one
IS - 12
M1 - 0084481
ER -