Decreased selenoprotein expression results in an altered immune response post influenza virus infection

Abstract

Previous work in our laboratory has demonstrated that host selenium (Se)-deficiency results in greater lung pathology and altered immune function in mice infected with influenza virus. Because selenoproteins play a key role in determining the oxidant status of the host, we utilized a transgenic mouse line, Sec tRNA[Ser]Sec (i6A), wherein the expressed tRNA product lacks a highly modified nucleoside, isopentenyladenosine (i6A), at position 37. The levels of selenoproteins are decreased in these mice in a protein and tissue specific manner. Male i6A and wildtype (WT) mice were infected with influenza and sacrificed at 0, 2 and 7 days post infection (p.i.). Lung mRNA levels for innate and pro-inflammatory cytokines were increased with infection, but did not differ between groups. However, at d3 p.i. chemokine levels were increased in the i6A mice compared to WT. Additionally, interferon-γ was higher at d7 p.i. in the i6A mice and viral clearance slower. Despite the immune changes, lung pathology was not different in the i6A- mice compared with WT mice. 75Se labeling experiments demonstrated that glutathione peroxidase-1 (GPx-1) and thioredoxin reductase (TR), although greatly diminished in the lungs of i6A- mice, were not altered as a result of infection. GPx-1 activity in the lungs of the i6A mice was approximately 6-fold less compared with WT mice. In addition, the GPx-1 activity levels in the lungs of Se-deficient mice are 10-fold less than that seen in the i6A mice. These results suggest that although selenoproteins are important for immune function, there is a threshold of GPx-1 activity that can prevent an increase in lung pathology post influenza infection. Supported byNIH grant R01 AI055050 to MAB.