title: Murine cytomegalovirus downregulates interleukin-17 in mice with retrovirus-induced immunosuppression that are susceptible to experimental cytomegalovirus retinitis.
abstract: Interleukin-17 (IL-17), a pro-inflammatory cytokine produced by CD4+ Th17 cells, has been associated with the pathogenesis of several autoimmune diseases including uveitis. The fate of IL-17 during HIV/AIDS, however, remains unclear, and a possible role for IL-17 in the pathogenesis of AIDS-related diseases has not been investigated. Toward these ends, we performed studies using a well-established animal model of experimental murine cytomegalovirus (MCMV) retinitis that develops in C57/BL6 mice with retrovirus-induced immunosuppression (MAIDS). After establishing baseline levels for IL-17 production in whole splenic cells of healthy mice, we observed a significant increase in IL-17 mRNA levels in whole splenic cells of mice with MAIDS of 4-weeks (MAIDS-4), 8-weeks (MAIDS-8), and 10-weeks (MAIDS-10) duration. In contrast, enriched populations of splenic CD4+ T cells, splenic macrophages, and splenic neutrophils exhibited a reproducible decrease in levels of IL-17 mRNA during MAIDS progression. To explore a possible role for IL-17 during the pathogenesis of MAIDS-related MCMV retinitis, we first demonstrated constitutive IL-17 expression in retinal photoreceptor cells of uninfected eyes of healthy mice. Subsequent studies, however, revealed a significant decrease in intraocular levels of IL-17 mRNA and protein in MCMV-infected eyes of MAIDS-10 mice during retinitis development. That MCMV infection might cause a remarkable downregulation of IL-17 production was supported further by the finding that systemic MCMV infection of healthy, MAIDS-4, or MAIDS-10 mice also significantly decreased IL-17 mRNA production by splenic CD4+ T cells. Based on additional studies using IL-10 -/- mice infected systemically with MCMV and IL-10 -/- mice with MAIDS infected intraocularly with MCMV, we propose that MCMV infection downregulates IL-17 production via stimulation of suppressor of cytokine signaling (SOCS)-3 and interleukin-10.
authors: Department of Biology, Viral Immunology Center, Georgia State University, Atlanta, GA 30303, United States.
authors: Emily L
authors: EL
authors: Blalock
authors: Hsin
authors: H
authors: Chien
authors: Richard D
authors: RD
authors: Dix
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D017726:Cytomegalovirus Retinitis / Q000235:genetics / Q000276:immunology / Q000473:pathology* / Q000821:virology*; D018450:Disease Progression; D004198:Disease Susceptibility; D015536:Down-Regulation; D005123:Eye / Q000378:metabolism; D005260:Female; D007165:Immunosuppression Therapy; D020381:Interleukin-17 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016183:Murine Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D018146:Muromegalovirus / Q000502:physiology*; D009504:Neutrophils / Q000378:metabolism; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012190:Retroviridae / Q000502:physiology; D013154:Spleen / Q000378:metabolism / Q000473:pathology; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D020381:Interleukin-17; D012333:RNA, Messenger; C491590:Socs1 protein, mouse; C491411:Socs3 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins