serval:BIB_CE9836DB152C
Sirtuin 3 deficiency does not alter host defenses against bacterial and fungal infections.
10.1038/s41598-017-04263-x
000403643900006
28634345
Ciarlo
E.
author
Heinonen
T.
author
Lugrin
J.
author
Acha-Orbea
H.
author
Le Roy
D.
author
Auwerx
J.
author
Roger
T.
author
article
2017-06-20
Scientific reports
2045-2322
2045-2322
journal
7
1
3853
Sirtuin 3 (SIRT3) is the main mitochondrial deacetylase. SIRT3 regulates cell metabolism and redox homeostasis, and protects from aging and age-associated pathologies. SIRT3 may drive both oncogenic and tumor-suppressive effects. SIRT3 deficiency has been reported to promote chronic inflammation-related disorders, but whether SIRT3 impacts on innate immune responses and host defenses against infections remains essentially unknown. This aspect is of primary importance considering the great interest in developing SIRT3-targeted therapies. Using SIRT3 knockout mice, we show that SIRT3 deficiency does not affect immune cell development and microbial ligand-induced proliferation and cytokine production by splenocytes, macrophages and dendritic cells. Going well along with these observations, SIRT3 deficiency has no major impact on cytokine production, bacterial burden and survival of mice subjected to endotoxemia, Escherichia coli peritonitis, Klebsiella pneumoniae pneumonia, listeriosis and candidiasis of diverse severity. These data suggest that SIRT3 is not critical to fight infections and support the safety of SIRT3-directed therapies based on SIRT3 activators or inhibitors for treating metabolic, oncologic and neurodegenerative diseases without putting patients at risk of infection.
Animals
Bacterial Infections/genetics
Biomarkers
Dendritic Cells/immunology
Dendritic Cells/metabolism
Disease Resistance/genetics
Host-Pathogen Interactions/genetics
Humans
Immunophenotyping
Macrophages/immunology
Macrophages/metabolism
Mice
Mice, Knockout
Mycoses/genetics
Sirtuin 3/deficiency
Thymocytes/immunology
Thymocytes/metabolism
eng
60_published
true
peer-reviewed
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: epublish
University of Lausanne
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