IL-10 Mediated Regulation of Liver Inflammation during Acute Murine Cytomegalovirus Infection |
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Authors: | Pamela J Gaddi Meredith J Crane Masahito Kamanaka Richard A Flavell George S Yap Thais P Salazar-Mather |
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Affiliation: | Division of Biology and Medicine, Department of Molecular Microbiology and Immunology and Warren Alpert Medical School, Brown University, Providence, Rhode Island, United States of America. |
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Abstract: | Various cell types in both lymphoid and non-lymphoid tissues produce the anti-inflammatory cytokine interleukin (IL)-10 during murine cytomegalovirus (MCMV) infection. The functions of IL-10 in the liver during acute infection and the cells that generate this cytokine at this site have not been extensively investigated. In this study, we demonstrate that the production of IL-10 in the liver is elevated in C57BL/6 mice during late acute MCMV infection. Using IL-10 green fluorescence protein (GFP) reporter knock-in mice, designated IL-10-internal ribosomal entry site (IRES)-GFP-enhanced reporter (tiger), NK cells are identified as major IL-10 expressing cells in the liver after infection, along with T cells and other leukocytes. In the absence of IL-10, mice exhibit marked elevations in proinflammatory cytokines and in the numbers of mononuclear cells and lymphocytes infiltrating the liver during this infection. IL-10-deficiency also enhances liver injury without improving viral clearance from this site. Collectively, the results indicate that IL-10-producing cells in the liver provide protection from collateral injury by modulating the inflammatory response associated with MCMV infection. |
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