Decreased selenoprotein expression alters the immune response during influenza virus infection in mice.
Previous work from our laboratory 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 carrying a mutant selenocysteine (Sec) tRNA ([Ser]Sec) transgene (t-trspi(6)A(-)). The levels of selenoproteins are decreased in these mice in a protein- and tissue-specific manner. Male t-trspi(6)A(-) and wild-type (WT) mice were infected with influenza and killed at various time points postinfection (p.i.). Lung mRNA levels for innate and pro-inflammatory cytokines increased with infection but did not differ between groups. However, at d 2 p.i., chemokine levels were greater in the t-trspi(6)A(-) mice compared with WT mice. Additionally, IFN-gamma was higher at d 7 p.i. in the t-trspi(6)A(-) mice and viral clearance slower. Despite these immune system changes, lung pathology was similar in t-trspi(6)A(-) and WT mice. (75)Se labeling experiments demonstrated that glutathione peroxidase (GPX)-1 and thioredoxin reductase, although greatly diminished in the lungs of t-trspi(6)A(-) mice, were not altered as a result of infection. GPX-1 activity in the lungs of the t-trspi(6)A(-) mice was approximately 82% of the WT mice. In addition, the GPX-1 activity in the lungs of Se-deficient mice was 125% less than in the t-trspi(6)A(-) 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 during influenza infection.
Sheridan
Patricia A
PA
Department of Nutrition, University of North Carolina, Chapel Hill, NC 27599, USA.
Zhong
Nianxin
N
Carlson
Bradley A
BA
Perella
Christine M
CM
Hatfield
Dolph L
DL
Beck
Melinda A
MA
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology* / Q000302:isolation & purification; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009975:Orthomyxoviridae / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D012345:RNA, Transfer, Amino Acid-Specific / Q000235:genetics* / Q000276:immunology; D051140:Selenoproteins / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology; D014018:Tissue Distribution
D016207:Cytokines; D012345:RNA, Transfer, Amino Acid-Specific; D051140:Selenoproteins; C036928:tRNA, selenocysteine-