Abstract
Purpose: :
An interleukin-17 (IL-17)-producing CD4+ T-cell subset (Th17 cells) has been recognized to play a role in autoimmune diseases. Since a role for IL-17 in HIV/AIDS and other virus infections is unclear, we investigated its possible contribution to development of murine cytomegalovirus (MCMV) retinitis in mice with retrovirus-induced immunosuppression (MAIDS).
Methods: :
To determine the fate of IL-17 production during MAIDS progression in the absence or presence of systemic MCMV infection, total splenic cells and purified (>90%) splenic CD4+ T cells were collected from normal mice and uninfected or systemically infected C57BL/6 mice with MAIDS of 4 and 10-weeks duration. To explore IL-17 production vis-à-vis development of retinal necrosis during MAIDS, whole eyes were collected from MAIDS-4, MAIDS-8, and MAIDS-10 mice at 10 days after subretinal MCMV injection or medium (control). All splenic cell populations and whole eyes were subjected to real time RT-PCR assay for quantification of IL-17 mRNA, and whole eyes were analyzed by ELISA for IL-17 protein.
Results: :
Whereas a 25-fold increase in IL-17 mRNA levels was observed in total splenic cells during MAIDS progression, purified splenic CD4+ T cells showed a 13-fold decrease in IL-17 mRNA levels when compared with normal mice. Systemic MCMV infection of MAIDS-4 and MAIDS-10 mice also resulted in a significant decrease in IL-17 mRNA levels of purified splenic CD4+ T cells. MCMV-infected whole eyes collected from MAIDS-10 animals susceptible to retinitis showed detectable IL-17 mRNA and IL-17 protein levels (16.4 pg/ml), but at levels equivalent to IL-17 mRNA and IL-17 protein levels (21.3 pg/ml) in mock-infected eyes.
Conclusions: :
Since total splenic cells showed increased IL-17 mRNA levels, but purified splenic CD4+ T cells showed decreased IL-17 mRNA levels, a splenic cell population other than CD4+ T cells is a source for IL-17 during MAIDS. Although IL-17 was detected in MCMV-infected eyes susceptible to retinitis, levels were equivalent to those in mock-infected eyes. We conclude that a direct contribution of IL-17 to pathogenesis of MAIDS-related MCMV retinitis is minimal.
Keywords: cytomegalovirus • retinitis • microbial pathogenesis: experimental studies