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Emily L. Blalock, Hsin Chien, Richard D. Dix; Murine Cytomegalovirus Downregulates Interleukin-17 in Mice with Retrovirus-induced Immunosuppression that are Susceptible to Experimental Cytomegalovirus Retinitis. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2965.
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Interleukin-17 (IL-17) produced by Th17 CD4+ T-helper cells plays a key role in regulating various inflammatory mediators. We therefore hypothesized that IL-17 plays a role in pathogenesis of experimental murine cytomegalovirus (MCMV) retinitis in mice with retrovirus-induced immunosuppression (MAIDS).
Purified (>95%) CD4+ T cells were collected from spleens of groups of (i) uninfected healthy C57BL/6 mice, (ii) uninfected mice with MAIDS of 4-, 8-, or 10-weeks duration, (iii) MCMV-infected healthy mice, and (iv) MCMV-infected MAIDS-4 mice, and MAIDS-10 mice at 6 days after systemic (intraperitoneal) inoculation. Splenic CD4+ T cells from all animal groups were subjected to RT-PCR assay for quantification of IL-17 mRNA levels. Whole eyes were also collected from parallel groups of MAIDS-10 animals inoculated subretinally with MCMV or medium (control), and analyzed 10 days post infection by RT-PCR assay for quantification of intraocular IL-17 mRNA levels and by ELISA and immunostaining for detection and quantification of intraocular IL-17 protein.
When compared with IL-17 mRNA levels of splenic CD4+ T-cells from uninfected healthy mice, IL-17 mRNA levels of splenic CD4+ T-cells from uninfected MAIDS-4 mice were significantly increased by ~16-fold, but IL-17 mRNA levels of splenic CD4+ T-cells from MAIDS-8 and MAIDS-10 mice fell to levels equivalent to those of healthy mice. Surprisingly, systemic MCMV infection of both MAIDS-4 and MAIDS-10 mice resulted in a significant reduction of IL-17 mRNA levels. No differences in IL-17 mRNA levels, IL-17 protein levels, or patterns of IL-17 immunostaining were observed when MCMV-infected eyes were compared with mock-infected eyes. Intraocular IL-17 protein was not detected in unmanipulated eyes by immunostaining.
IL-17 plays no role in the pathogenesis of MAIDS-related MCMV retinitis. In fact, systemic MCMV infection appears to downregulate IL-17 production by splenic CD4+ T cells during MAIDS. Whether Th17 CD4+ T cells play a protective role in resistance to MCMV retinitis remains unclear.
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