title: EBI3 regulates the NK cell response to mouse cytomegalovirus infection.
abstract: Natural killer (NK) cells are key mediators in the control of cytomegalovirus infection. Here, we show that Epstein-Barr virus-induced 3 (EBI3) is expressed by human NK cells after NKG2D or IL-12 plus IL-18 stimulation and by mouse NK cells during mouse cytomegalovirus (MCMV) infection. The induction of EBI3 protein expression in mouse NK cells is a late activation event. Thus, early activation events of NK cells, such as IFNγ production and CD69 expression, were not affected in EBI3-deficient (Ebi3-/-) C57BL/6 (B6) mice during MCMV infection. Furthermore, comparable levels of early viral replication in spleen and liver were observed in MCMV-infectedEbi3-/-and wild-type (WT) B6 mice. Interestingly, the viral load in salivary glands and oral lavage was strongly decreased in the MCMV-infectedEbi3-/-B6 mice, suggesting that EBI3 plays a role in the establishment of MCMV latency. We detected a decrease in the sustained IL-10 production by NK cells and lower serum levels of IL-10 in the MCMV-infectedEbi3-/-B6 mice. Furthermore, we observed an increase in dendritic cell maturation markers and an increase in activated CD8+T cells. Thus, EBI3 dampens the immune response against MCMV infection, resulting in prolonged viral persistence.
authors.affiliation: Department of Microbiology and Immunology, University of California, San Francisco, CA 94143.
authors.forename: Helle
authors.initials: H
authors.lastname: Jensen
authors.affiliation: Department of Microbiology and Immunology, Stanford University, Palo Alto, CA 94304.
authors.forename: Shih-Yu
authors.initials: SY
authors.lastname: Chen
authors.affiliation: Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby DK-2800, Denmark.
authors.forename: Lasse
authors.initials: L
authors.lastname: Folkersen
authors.affiliation: Department of Microbiology and Immunology, Stanford University, Palo Alto, CA 94304.
authors.forename: Garry P
authors.initials: GP
authors.lastname: Nolan
authors.affiliation: Department of Microbiology and Immunology, University of California, San Francisco, CA 94143; lewis.lanier@ucsf.edu.|Parker Institute for Cancer Immunotherapy, San Francisco, CA 94143.
authors.forename: Lewis L
authors.initials: LL
authors.lastname: Lanier
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D015870:Gene Expression / Q000276:immunology; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism; D020382:Interleukin-18 / Q000276:immunology / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015778:Minor Histocompatibility Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018146:Muromegalovirus / Q000276:immunology* / Q000502:physiology; D018121:Receptors, Cytokine / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: C499601:Ebi3 protein, mouse; D020382:Interleukin-18; D015778:Minor Histocompatibility Antigens; D018121:Receptors, Cytokine; D018664:Interleukin-12
keywords: EBI3; cytomegalovirus; natural killer cell