Sirtuins and Immuno-Metabolism of Sepsis

Wang, Xianfeng; Buechler, Nancy L.; Woodruff, Alan G.; Long, David L.; Zabalawi, Manal; Yoza, Barbara K.; McCall, Charles E.; Vachharajani, Vidula

doi:10.3390/ijms19092738

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Sirtuins and Immuno-Metabolism of Sepsis

by

Xianfeng Wang

¹,

Nancy L. Buechler

¹,

Alan G. Woodruff

¹,

David L. Long

²,

Manal Zabalawi

²,

Barbara K. Yoza

^2,3,

Charles E. McCall

^1,2,* and

Vidula Vachharajani

^1,2,*

¹

Departments of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA

²

Departments of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA

³

Departments of Surgery, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA

^*

Authors to whom correspondence should be addressed.

Int. J. Mol. Sci. 2018, 19(9), 2738; https://doi.org/10.3390/ijms19092738

Submission received: 16 August 2018 / Revised: 6 September 2018 / Accepted: 8 September 2018 / Published: 13 September 2018

(This article belongs to the Special Issue Sirtuins and Epigenetics in Aging and Diseases)

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Abstract

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.

Keywords: sepsis; septic shock; hyper-inflammation; immunosuppression

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MDPI and ACS Style

Wang, X.; Buechler, N.L.; Woodruff, A.G.; Long, D.L.; Zabalawi, M.; Yoza, B.K.; McCall, C.E.; Vachharajani, V. Sirtuins and Immuno-Metabolism of Sepsis. Int. J. Mol. Sci. 2018, 19, 2738. https://doi.org/10.3390/ijms19092738

AMA Style

Wang X, Buechler NL, Woodruff AG, Long DL, Zabalawi M, Yoza BK, McCall CE, Vachharajani V. Sirtuins and Immuno-Metabolism of Sepsis. International Journal of Molecular Sciences. 2018; 19(9):2738. https://doi.org/10.3390/ijms19092738

Chicago/Turabian Style

Wang, Xianfeng, Nancy L. Buechler, Alan G. Woodruff, David L. Long, Manal Zabalawi, Barbara K. Yoza, Charles E. McCall, and Vidula Vachharajani. 2018. "Sirtuins and Immuno-Metabolism of Sepsis" International Journal of Molecular Sciences 19, no. 9: 2738. https://doi.org/10.3390/ijms19092738

APA Style

Wang, X., Buechler, N. L., Woodruff, A. G., Long, D. L., Zabalawi, M., Yoza, B. K., McCall, C. E., & Vachharajani, V. (2018). Sirtuins and Immuno-Metabolism of Sepsis. International Journal of Molecular Sciences, 19(9), 2738. https://doi.org/10.3390/ijms19092738

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