title: Myeloid cell sirtuin-1 expression does not alter host immune responses to Gram-negative endotoxemia or Gram-positive bacterial infection.
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 gram-negative 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.
authors.affiliation: Pulmonary Critical Care Section, Veterans Affairs San Diego Healthcare System, San Diego, California, United States of America ; Department of Medicine, University of California San Diego, San Diego, California, United States of America.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Crotty Alexander
authors.affiliation: Pulmonary Critical Care Section, Veterans Affairs San Diego Healthcare System, San Diego, California, United States of America ; Department of Medicine, University of California San Diego, San Diego, California, United States of America.
authors.forename: Brenda J
authors.initials: BJ
authors.lastname: Marsh
authors.affiliation: Department of Pediatrics, University of California San Diego, San Diego, California, United States of America.
authors.forename: Anjuli M
authors.initials: AM
authors.lastname: Timmer
authors.affiliation: Department of Pediatrics, University of California San Diego, San Diego, California, United States of America.
authors.forename: Ann E
authors.initials: AE
authors.lastname: Lin
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
authors.forename: Kayvan
authors.initials: K
authors.lastname: Zainabadi
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Czopik
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
authors.forename: Leonard
authors.initials: L
authors.lastname: Guarente
authors.affiliation: Department of Pediatrics, University of California San Diego, San Diego, California, United States of America ; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, San Diego, California, United States of America.
authors.forename: Victor
authors.initials: V
authors.lastname: Nizet
mesh_terms: D000818:Animals; D016470:Bacteremia / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D019446:Endotoxemia / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology*; D055785:Gene Knockdown Techniques; D016908:Gram-Positive Bacterial Infections / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018922:HL-60 Cells; D006801:Humans; D051379:Mice; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D056564:Sirtuin 1 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*
chemical_list: C447939:SIRT1 protein, human; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1