title: Sources and signals regulating type I interferon production: lessons learned from cytomegalovirus.
abstract: Type I interferons (IFN-αβ) are pleiotropic cytokines critical for antiviral host defense, and the timing and magnitude of their production involve a complex interplay between host and pathogen factors. Mouse cytomegalovirus (a β-herpesvirus) is a persistent virus that induces a biphasic IFN-αβ response during the first days of infection. The cell types and molecular mechanisms governing these 2 phases are unique, with splenic stromal cells being a major source of initial IFN-αβ, requiring communication with B cells expressing lymphotoxin, a tumor necrosis factor family cytokine. Here we review the factors that regulate this lymphotoxin-IFN-αβ "axis" during cytomegalovirus infection, highlight how stroma-derived IFN-αβ contributes in other models, and discuss how deregulation of this axis can lead to pathology in some settings.
authors.affiliation: Division of Immune Regulation, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA.
authors.forename: Shilpi
authors.initials: S
authors.lastname: Verma
authors.forename: Chris A
authors.initials: CA
authors.lastname: Benedict
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D003587:Cytomegalovirus / Q000502:physiology*; D006566:Herpesviridae Infections / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D007370:Interferon Type I / Q000096:biosynthesis* / Q000276:immunology; D053361:Lymphotoxin alpha1, beta2 Heterotrimer / Q000378:metabolism; D053259:Lymphotoxin beta Receptor / Q000378:metabolism; D015398:Signal Transduction; D017154:Stromal Cells / Q000378:metabolism / Q000821:virology
chemical_list: D007370:Interferon Type I; D053361:Lymphotoxin alpha1, beta2 Heterotrimer; D053259:Lymphotoxin beta Receptor