Sirtuins and Immuno-Metabolism of Sepsis

• Main Authors: Xianfeng Wang, Nancy L. Buechler, Alan G. Woodruff, David L. Long, Manal Zabalawi, Barbara K. Yoza, Charles E. McCall, Vidula Vachharajani
• Format: Article
• Language: English
• Published: MDPI AG 2018-09-01
• Series: International Journal of Molecular Sciences
• Subjects: sepsis; septic shock; hyper-inflammation; immunosuppression
• Online Access: http://www.mdpi.com/1422-0067/19/9/2738

Sepsis and septic shock are the leading causes of death in non-coronary intensive care units worldwide. During sepsis-associated immune dysfunction, the early/hyper-inflammatory phase transitions to a late/hypo-inflammatory phase as sepsis progresses. The majority of sepsis-related deaths occur during the hypo-inflammatory phase. There are no phase-specific therapies currently available for clinical use in sepsis. Metabolic rewiring directs the transition from hyper-inflammatory to hypo-inflammatory immune responses to protect homeostasis during sepsis inflammation, but the mechanisms underlying this immuno-metabolic network are unclear. Here, we review the roles of NAD+ sensing Sirtuin (SIRT) family members in controlling immunometabolic rewiring during the acute systemic inflammatory response associated with sepsis. We discuss individual contributions among family members SIRT 1, 2, 3, 4 and 6 in regulating the metabolic switch between carbohydrate-fueled hyper-inflammation to lipid-fueled hypo-inflammation. We further highlight the role of SIRT1 and SIRT2 as potential “druggable” targets for promoting immunometabolic homeostasis and increasing sepsis survival.