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

First Author  Heinonen T Year  2018
Journal  Front Immunol Volume  9
Pages  2675 PubMed ID  30515162
Mgi Jnum  J:337315 Mgi Id  MGI:6871624
Doi  10.3389/fimmu.2018.02675 Citation  Heinonen T, et al. (2018) Sirtuin 5 Deficiency Does Not Compromise Innate Immune Responses to Bacterial Infections. Front Immunol 9:2675
abstractText  Sirtuin 5 (SIRT5) is a member of the family of NAD(+)-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.
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