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Emily L. Blalock, Hsin Chien, Richard D. Dix; Murine Cytomegalovirus (MCMV) Downregulates Interleukin-17 via Increased Interleukin-10 Expression in Mice with Retrovirus-induced Immunuosuppression (MAIDS) that are Susceptible to Experimental Cytomegalovirus Retinitis. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6226.
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We have shown previously that IL-17 mRNA and protein levels are downregulated during ocular and systemic MCMV infection of mice with MAIDS suggesting that MCMV infection downregulates IL-17 expression. We therefore investigated the mechanism(s) by which MCMV downregulates IL-17 production. Since the IL-10R expressed on Th17 cells negatively regulates IL-17 secretion via IL-10 binding, we hypothesized that loss of IL-10 would result in increased IL-17 mRNA and protein levels during MCMV infection.
IL-10 mRNA expression levels during MAIDS were determined by analyzing splenic cells from mice with MAIDS of 4-week (MAIDS-4) and 10-week duration (MAIDS-10) via real time RT-PCR assay. IL-10 mRNA expression levels were also analyzed in the eyes of MAIDS-4 (retinitis resistant) and MAIDS-10 (retinitis susceptible) mice on days 3, 6, and 10 after subretinal MCMV infection. IL-17 mRNA and protein levels were analyzed in whole splenic and splenic CD4+ T-cell populations of IL-10KO and wildtype mice during systemic MCMV infection by real time RT-PCR assay and ELISA.
IL-10 mRNA levels were significantly increased during progression of MAIDS. Ocular IL-10 mRNA levels peaked at day 6 after subretinal MCMV infection in MAIDS-4 and MAIDS-10 mice, although levels were significantly higher in MAIDS-10 mice. While IL-17 mRNA expression levels in splenic CD4+ T-cells were significantly reduced in MCMV-infected wildtype and IL-10KO mice, IL-17 mRNA levels were elevated in IL-10KO MCMV-infected mice (~2-fold higher), but not significantly.
Increased IL-10 mRNA during MAIDS progression and ocular MCMV infection correlated with IL-17 downregulation in CD4+ T-cells during both systemic and ocular MCMV infection. IL-10 knockdown resulted in a partial restoration of IL-17 levels during MCMV infection. Other factors may therefore contribute to IL-17 downregulation during MCMV infection.
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