title: Cutting edge: stage-specific requirement of IL-18 for antiviral NK cell expansion.
abstract: Although NK cells are considered part of the innate immune system, recent studies have demonstrated the ability of Ag-experienced NK cells to become long-lived and contribute to potent recall responses similar to T and B cells. The precise signals that promote the generation of a long-lived NK cell response are largely undefined. In this article, we demonstrate that NK cells require IL-18 signaling to generate a robust primary response during mouse CMV (MCMV) infection but do not require this signal for memory cell maintenance or recall responses. IL-12 signaling and STAT4 in activated NK cells increased the expression of the adaptor protein MyD88, which mediates signaling downstream of the IL-18 and IL-1 receptors. During MCMV infection, NK cells required MyD88, but not IL-1R, for optimal expansion. Thus, an IL-18-MyD88 signaling axis facilitates the prolific expansion of NK cells in response to primary viral infection, but not recall responses.
authors.affiliation: Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065.
authors.forename: Sharline
authors.initials: S
authors.lastname: Madera
authors.affiliation: Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065 sunj@mskcc.org.
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Sun
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology; D000818:Animals; D047369:Chromatin Immunoprecipitation; D005434:Flow Cytometry; D006566:Herpesviridae Infections / Q000276:immunology; D007113:Immunity, Innate / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology; D020382:Interleukin-18 / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D018146:Muromegalovirus / Q000276:immunology; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology*
chemical_list: D020382:Interleukin-18; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88