Sirtuin 5 Deficiency Does Not Compromise Innate Immune Responses to Bacterial Infections.

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State: Public
Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_39701912842C
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Sirtuin 5 Deficiency Does Not Compromise Innate Immune Responses to Bacterial Infections.
Journal
Frontiers in immunology
Author(s)
Heinonen T., Ciarlo E., Théroude C., Pelekanou A., Herderschee J., Le Roy D., Roger T.
ISSN
1664-3224 (Electronic)
ISSN-L
1664-3224
Publication state
Published
Issued date
2018
Peer-reviewed
Oui
Volume
9
Pages
2675
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
Sirtuin 5 (SIRT5) is a member of the family of NAD <sup>+</sup> -dependent lysine/histone deacetylases. SIRT5 resides mainly in the mitochondria where it catalyzes deacetylation, demalonylation, desuccinylation, and deglutarylation of lysine to regulate metabolic and oxidative stress response pathways. Pharmacologic inhibitors of SIRT5 are under development for oncologic conditions, but nothing is known about the impact of SIRT5 on antimicrobial innate immune defenses. Using SIRT5 knockout mice, we show that SIRT5 deficiency does not affect immune cell development, cytokine production and proliferation by macrophages and splenocytes exposed to microbial and immunological stimuli. Moreover, preclinical models suggest that SIRT5 deficiency does not worsen endotoxemia, Klebsiella pneumoniae and Streptococcus pneumoniae pneumonia, Escherichia coli peritonitis, listeriosis, and staphylococcal infection. Altogether, these data support the safety profile in terms of susceptibility to infections of SIRT5 inhibitors under development.
Keywords
Animals, Bacteria/immunology, Bacterial Infections/genetics, Bacterial Infections/immunology, Immunity, Innate, Mice, Mice, Knockout, Sirtuins/deficiency, Sirtuins/immunology, cytokine, endotoxemia, histone deacetylase, innate immunity, macrophage, metabolism, sepsis, sirtuin
Pubmed
Web of science
Open Access
Yes
Create date
13/12/2018 16:45
Last modification date
04/10/2019 6:08
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