J. M. Reel, Hazzar M. Abysalamah, Christopher R. Lupfer
May 1, 2020
Citations
0
Influential Citations
0
Citations
Journal
The Journal of Immunology
Abstract
Pyruvate is a key metabolite for energy synthesis. After the production of pyruvate through glycolysis, the molecule is shuttled into the mitochondria. Once there, it is modified for use in the TCA cycle and the energy derived from pyruvate is eventually converted into ATP. While pyruvate is a key metabolite, it also appears to have anti-inflammatory properties. In models of sterile inflammation, like ischemia, pyruvate limits inflammation. We observed that infecting murine bone marrow derived macrophages (BMDM) with influenza A virus (IAV) and treating those macrophages with sodium pyruvate results in lower inflammasome activation and reactive oxygen species (ROS) production. However, this was specific to IAV infection as inflammasome activation and ROS were not affected by sodium pyruvate during E. coli infection or lipopolysaccharide (LPS) and ATP treatment of BMDMs. Our results show that IAV induces a potent and unique metabolic reprograming of infected cells. The addition of sodium pyruvate facilitates ATP production, which correlates with less mitochondrial damage and reduced inflammasome activation. Thus, pyruvate deserves additional examination as an anti-inflammatory treatment in diseases where mitochondrial metabolic stress is a factor.