The Immune Response to Influenza is Suppressed by the Synthetic Food Additive and Nrf2 Activator, tert-butylhydroquinone (tBHQ)

Influenza virus infections have been a persistent threat to society, causing up to 650,000 respiratory deaths annually world-wide. The United States alone suffered 80,000 influenza-related deaths during the 2017/18 flu season. Although vaccine coverage has increased in the U.S., this has not correlated with a decline in influenza-related infections or deaths. Accordingly, there is significant interest in the identification of environmental factors which may contribute to influenza burden and/or reduce vaccine efficacy. Previous work from our laboratory demonstrated that a widely-used food additive, -tert-butylhydroquinone (tBHQ), impairs human CD4+ T cell activation and murine TH1 cell polarization (important in anti-viral defense) ex vivo. These effects occurred through activation of the stress-activated transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2), as evidenced using Nrf2-deficient human and murine models. Under basal conditions, Nrf2 is repressed in the cytosol by its repres...