SIRT5 is important for bacterial infection by regulating insulin secretion and glucose homeostasis
- PDF / 441,499 Bytes
- 6 Pages / 595.276 x 785.197 pts Page_size
- 7 Downloads / 174 Views
Protein & Cell
LETTER
Dear Editor, Recent studies indicate that cellular metabolism plays a key role in supporting immune cell development, maintenance and function (Norata et al., 2015). For example, sensing of microbial ligands by macrophages triggers increased glucose metabolism, which delivers energy to support antimicrobial inflammation and the production of cytokines. This effect further enhances the generation of mitochondrial reactive oxygen species (ROS) to fight infections. Tucey et al. show that maintaining host glucose homeostasis is important to prevent life-threatening fungal infection (Tucey et al., 2018). This phenomenon emerges as a bedrock of the emerging concept of how metabolism and immunity are integrated based on bioenergy requirements. Sirtuins contribute to dynamic shifts in immunity, metabolism, and bioenergetics during inflammation (Vachharajani et al., 2016). Therefore, targeting Sirtuins is likely to deliver new opportunities for manipulating immunometabolism as an anti-inflammatory strategy. However, better understanding of Sirtuin biology and its role in regulation of inflammation is in its infancy. SIRT1 acts as a key control point for regulating metabolism and inflammatory outputs from T cells (Liu et al., 2012). In our previous work, we demonstrated that SIRT5 plays an important role in preventing dextran sulfate sodium (DSS)-induced colitis by regulating glycolysis in macrophages (Wang et al., 2017). Inflammation in DSS-induced colitis is not of infectious origin. We would like to know the function of SIRT5 in infection-induced inflammation and host defense. To study the role of SIRT5 in infection response, we treated littermate wild-type (WT) and Sirt5-deficient (Sirt5−/−) mice with lipopolysaccharide (LPS). When Sirt5−/− mice were treated with LPS for 3 h, the level of blood glucose decreased and the level of serum insulin increased significantly (Fig. 1A and 1B), accompanied with increased concentration of circulating IL-1β (Fig. 1C). Peritoneal macrophages (PMs) from Sirt5−/− mice treated with LPS also expressed higher level of Il-1β mRNA and secreted more IL1β (Fig. S1A and S1B). These results indicated that SIRT5 has a potential role in regulating glucose homeostasis and
© The Author(s) 2020
Sirt5 deficiency boosts IL-1β production in inflammatory response. Then, we wanted to know the source of the elevated IL1β. The gating strategies of flow cytometry for immune cells have been shown in Fig. S1C. We found that the F4/80+/ CD11b+ macrophages accounted for the largest proportion of the immune cells isolated from peritoneal cavity of Sirt5−/− mice treated with LPS (Fig. S1D), which is consistent with a previous interesting report (Dror et al., 2017). Depletion of the peritoneal macrophages by intraperitoneal injection of clodronate liposomes (Fig. S1E) eliminated the effect induced by LPS treatment in Sirt5−/− mice. The blood glucose, circulating insulin and IL-1β level in LPS-treated Sirt5−/− mice showed no significant difference with that in WT mice (Fig. 1D–F). Therefore, LPS induced
Data Loading...
