Pyruvate affects inflammatory responses of macrophages during influenza A virus infection

Abstract

Pyruvate is the end product of glycolysis and transported into the mitochondria for use in the tricarboxylic acid (TCA) cycle. It is also a common additive in cell culture media. We discovered that inclusion of sodium pyruvate in culture media during infection of mouse bone marrow derived macrophages with influenza A virus impaired cytokine production (IL-6, IL-1β, and TNF-α). Sodium pyruvate did not inhibit viral RNA replication. Instead, the addition of sodium pyruvate alters cellular metabolism and diminished mitochondrial reactive oxygen species (ROS) production and lowered immune signaling. Overall, sodium pyruvate affects the immune response produced by macrophages but does not inhibit virus replication.

Sodium Pyruvate Ameliorates Influenza A Virus InfectionIn Vivo

“…As previously reported in vitro [23], we also observed significantly less IL-1β levels in the lungs of N115 treated mice ( Figure 4A ). Despite lower IL-1β levels, most leukocyte numbers were similar in the lungs of N115 and PBS treated mice, except for inflammatory monocyte numbers, which were elevated in the N115 mice ( Figure 4B-C ).…”

“…Our previous research with NaPyr in vitro established its immunomodulatory properties [23]. We, therefore, examined its effects in mice infected with IAV.…”

“…Bone and tissue inflammation models have shown that Pyr treatment lead to less destructive results of disease via anti-inflammatory properties [21, 22]. In relation to infectious disease, sodium pyruvate (NaPyr) (C 3 H 4 NaO 3 ) can improve herpes simplex 2 virus infection in vivo , and our lab recently reported that NaPyr can regulate inflammation during IAV infection in vitro [23, 24].…”

“…In our previous study, we observed in mouse bone marrow derived macrophages (BMDM), that NaPyr has anti-inflammatory capabilities through altered metabolism [23]. The addition of NaPyr to BMDM decreased mitochondrial damage in response to IAV infection.…”

Sodium Pyruvate Ameliorates Influenza A Virus Infection In Vivo

“…Bone and tissue inflammation models have shown that Pyr treatment leads to less destructive disease via anti-inflammatory properties [29,30]. In relation to infectious disease, sodium pyruvate (NaPyr) (C 3 H 4 NaO 3 ) can improve herpes simplex 2 virus infection in vivo, and our lab recently reported that NaPyr can regulate inflammation during IAV infection in vitro [31,32].…”