Selenium Deficiency Induced an Altered Immune Response and Increased Survival Following Influenza A/Puerto Rico/8/34 Infection

Abstract

This study was designed to determine the effect of selenium (Se) deficiency on the immune response to infection with a virulent strain of influenza virus, influenza A/Puerto Rico/8/34. Previous work in our laboratory demonstrated that Se-deficient mice infected with a mild strain of influenza virus, influenza A/ Bangkok/1/79, developed much more severe lung pathology compared with Se-adequate mice. Immune function was altered in the Se-deficient mice, and the viral genome changed to a more virulent genotype. In this study, we tested whether Se deficiency would have a similar effect on mice infected with a more virulent, mouse-adapted strain of influenza virus. Three-week-old male mice were fed Se-adequate or Se-deficient diet for 4 weeks before inoculation with influenza A/PR8/34. There was no difference in lung influenza viral titer between Se-deficient and Se-adequate mice. Se-deficient mice had less macrophage inflammatory protein 1α (MIP-1α) and regulated upon activation, normal T cell expressed and secreted (RANTES) production at the transcriptional and protein level in the lung postinfection. Se-deficient mice also had higher levels of IL-2 expression followed by a higher level of IL-4 expression in the lung. At Day 7 postinfection, there was no death in the Se-deficient group compared with 50% of the mice dying in the Se-adequate group. Sequencing of the virus isolated from infected Se-adequate and Se-deficient mice did not detect viral genome mutations in either group. This study demonstrated that Se-deficient mice had an altered immune response to an infection with a virulent strain of influenza virus. This altered immune response was beneficial for protecting the mice from influenza virus-induced mortality.