title: Differential responses of immune cells to type I interferon contribute to host resistance to viral infection.
abstract: Type I interferons (IFNs) are central to antiviral defense, but how they orchestrate immune cell function is incompletely understood. We determined that IFNs produced during murine cytomegalovirus (MCMV) infection differentially affect dendritic cells (DCs) and natural killer (NK) cells. IFNs induce cell-intrinsic responses in DCs, activating antiproliferative, antiviral, and lymphocyte-activating gene networks, consistent with high activity of the transcription factor STAT1 in these cells. By comparison, NK cells exhibit lower STAT1 expression and reduced IFN responsiveness. Rather, IFNs indirectly affect NK cells by inducing IL-15, which activates the transcription factor E2F and stimulates genes promoting cell expansion. IFN cell-intrinsic responses are necessary in DCs, but not NK cells, for MCMV resistance. Thus, sensitivity to IFN-induced cytokines and differences in IFN receptor signaling program immune cells to mount distinct responses that promote viral control.
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, UNIV UM2, Aix-Marseille Université, Parc scientifique et technologique de Luminy, 13288 Marseille, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Baranek
authors.forename: Thien-Phong Vu
authors.initials: TP
authors.lastname: Manh
authors.forename: Yannick
authors.initials: Y
authors.lastname: Alexandre
authors.forename: Muhammad Ahmad
authors.initials: MA
authors.lastname: Maqbool
authors.forename: Joaquin Zacarias
authors.initials: JZ
authors.lastname: Cabeza
authors.forename: Elena
authors.initials: E
authors.lastname: Tomasello
authors.forename: Karine
authors.initials: K
authors.lastname: Crozat
authors.forename: Gilles
authors.initials: G
authors.lastname: Bessou
authors.forename: Nicolas
authors.initials: N
authors.lastname: Zucchini
authors.forename: Scott H
authors.initials: SH
authors.lastname: Robbins
authors.forename: Eric
authors.initials: E
authors.lastname: Vivier
authors.forename: Ulrich
authors.initials: U
authors.lastname: Kalinke
authors.forename: Pierre
authors.initials: P
authors.lastname: Ferrier
authors.forename: Marc
authors.initials: M
authors.lastname: Dalod
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006566:Herpesviridae Infections / Q000276:immunology / Q000662:veterinary; D007370:Interferon Type I / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D018146:Muromegalovirus / Q000276:immunology*; D015398:Signal Transduction
chemical_list: D007370:Interferon Type I