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Richard Dix, Christine Alston, Emily Blalock, Jessica Fleming, Hsin Chien; Infiltrating granulocytes and resident Muller cells are major sources for suppressor of cytokine signaling (SOCS)1 and SOCS3 production during murine cytomegalovirus (MCMV) retinitis in mice with retrovirus-induced immunosuppression (MAIDS). Invest. Ophthalmol. Vis. Sci. 2013;54(15):126.
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SOCS family proteins govern the regulation of immune responses to pathogen invasion by a negative feedback regulatory mechanism to prevent cytokine over-expression. SOCS1 is an inhibitor of interferon signaling, whereas SOCS3 regulates the divergent actions of IL-6 and IL-10. We have shown previously that SOCS1 and SOCS3 mRNAs and proteins are upregulated in MCMV-infected eyes with retinitis during MAIDS. These findings prompted us to define the cell types that serve as sources for SOCS1 and SOCS3 production.
Groups of C57BL/6 mice with MAIDS were injected subretinally with MCMV or mock injected (control). At 6 and 10 days postinfection, whole eyes were collected, cryostat sectioned, and subjected to immunostaining for detection and localization of SOCS1 or SOCS3 production to specific cells types within the retina. These included infiltrating macrophages (F4/80), infiltrating granulocytes (neutrophils) (Ly-6G), resident Muller cells (GFAP), and resident microglial cells (Iba-1).
When compared with mock-infected eyes, MCMV-infected eyes of MAIDS mice that showed retinitis exhibited expression of SOCS1 and SOCS3 in infiltrating macrophages, infiltrating granulocytes, resident Muller cells, and resident microglia cells of the retina at 10 days postinfection. Quantification of SOCS1 and SOCS3 production by these cells suggested infiltrating granulocytes ≈ Muller cells > microglial cells > infiltrating macrophages.
The sources of SOCS1 or SOCS3 production in the retina during development of MAIDS-related MCMV retinitis includes infiltrating granulocytes and infiltrating macrophages as well as resident Muller cells and resident microglial cells. Of these cell types, however, major sources for SOCS1 and SOCS3 production are infiltrating granulocytes and resident Muller cells.
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