title: Hematopoietic cell-derived interferon controls viral replication and virus-induced disease.
abstract: Type I interferon (IFN-I) strongly inhibits viral replication and is a crucial factor in controlling virus infections and diseases. Cellular activation through pattern recognition receptors induces interferon production in a wide variety of hematopoietic and nonhematopoietic cell types, including dendritic cells, fibroblasts, hepatocytes, and cells of neuronal origin. The relative contribution of hematopoietic and nonhematopoietic cells to the overall interferon response is an important issue which has not been fully addressed. Using irf7(-/-) and wild-type bone marrow chimeras we analyzed the contribution of IFN-I from bone marrow-derived sources in the control of viral infections and immunopathology in mice. We found that during systemic cytopathic virus infection, hematopoietic cells were essential for production of IFN-I, inhibition of viral spread to peripheral organs, and limiting cell damage. In a model of autoimmune diabetes induced by noncytopathic virus infection, hematopoietic cell-derived IFN-I was essential for CD8(+) T cell-dependent cytotoxicity in pancreatic beta-islet cells and induction of diabetes. These data suggest that during systemic viral infection primarily hematopoietic cell-derived IFN-I controls viral replication and viral-induced disease.
authors.affiliation: Institute of Experimental Immunology, University Hospital of Zurich, Zurich, Switzerland. philipp.lang@gmx.net
authors.forename: Philipp A
authors.initials: PA
authors.lastname: Lang
authors.forename: Luisa
authors.initials: L
authors.lastname: Cervantes-Barragan
authors.forename: Admar
authors.initials: A
authors.lastname: Verschoor
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Navarini
authors.forename: Mike
authors.initials: M
authors.lastname: Recher
authors.forename: Marc
authors.initials: M
authors.lastname: Pellegrini
authors.forename: Lukas
authors.initials: L
authors.lastname: Flatz
authors.forename: Andreas
authors.initials: A
authors.lastname: Bergthaler
authors.forename: Kenya
authors.initials: K
authors.lastname: Honda
authors.forename: Burkhard
authors.initials: B
authors.lastname: Ludewig
authors.forename: Pamela S
authors.initials: PS
authors.lastname: Ohashi
authors.forename: Karl S
authors.initials: KS
authors.lastname: Lang
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology / Q000821:virology; D006412:Hematopoietic Stem Cells / Q000276:immunology* / Q000821:virology; D050417:Insulin-Secreting Cells / Q000276:immunology / Q000821:virology; D050839:Interferon Regulatory Factor-7 / Q000235:genetics / Q000276:immunology*; D007370:Interferon Type I / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D012327:RNA Virus Infections / Q000235:genetics / Q000276:immunology*; D012328:RNA Viruses / Q000276:immunology*; D014709:Vero Cells; D014779:Virus Replication / Q000235:genetics / Q000276:immunology*
chemical_list: D050839:Interferon Regulatory Factor-7; D007370:Interferon Type I; C494235:Irf7 protein, mouse