title: IL-10 mediated regulation of liver inflammation during acute murine cytomegalovirus infection.
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.
authors.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.
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Gaddi
authors.forename: Meredith J
authors.initials: MJ
authors.lastname: Crane
authors.forename: Masahito
authors.initials: M
authors.lastname: Kamanaka
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
authors.forename: George S
authors.initials: GS
authors.lastname: Yap
authors.forename: Thais P
authors.initials: TP
authors.lastname: Salazar-Mather
mesh_terms: D000208:Acute Disease; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D018414:CD8-Positive T-Lymphocytes; D018925:Chemokines / Q000096:biosynthesis; D003586:Cytomegalovirus Infections / Q000097:blood / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D007249:Inflammation / Q000097:blood / Q000150:complications / Q000382:microbiology / Q000473:pathology*; D018836:Inflammation Mediators / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis / Q000172:deficiency / Q000378:metabolism*; D007962:Leukocytes / Q000378:metabolism; D008099:Liver / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D018146:Muromegalovirus / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019562:Viral Load
chemical_list: D018925:Chemokines; C556062:IL10 protein, mouse; D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma; D000410:Alanine Transaminase