title: Activation of the type I interferon pathway is enhanced in response to human neuronal differentiation.
abstract: Despite the crucial role of innate immunity in preventing or controlling pathogen-induced damage in most, if not all, cell types, very little is known about the activity of this essential defense system in central nervous system neurons, especially in humans. In this report we use both an established neuronal cell line model and an embryonic stem cell-based system to examine human neuronal innate immunity and responses to neurotropic alphavirus infection in cultured cells. We demonstrate that neuronal differentiation is associated with increased expression of crucial type I interferon signaling pathway components, including interferon regulatory factor-9 and an interferon receptor heterodimer subunit, which results in enhanced interferon stimulation and subsequent heightened antiviral activity and cytoprotective responses against neurotropic alphaviruses such as western equine encephalitis virus. These results identify important differentiation-dependent changes in innate immune system function that control cell-autonomous neuronal responses. Furthermore, this work demonstrates the utility of human embryonic stem cell-derived cultures as a platform to study the interactions between innate immunity, virus infection, and pathogenesis in central nervous system neurons.
authors.affiliation: Department of Microbiology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
authors.forename: Jocelyn R
authors.initials: JR
authors.lastname: Farmer
authors.forename: Kate M
authors.initials: KM
authors.lastname: Altschaefl
authors.forename: K Sue
authors.initials: KS
authors.lastname: O'Shea
authors.forename: David J
authors.initials: DJ
authors.lastname: Miller
mesh_terms: D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D015870:Gene Expression; D023061:Gene Order; D006801:Humans; D007113:Immunity, Innate; D007370:Interferon Type I / Q000276:immunology / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D053633:Receptor, Interferon alpha-beta / Q000235:genetics / Q000378:metabolism; D050795:STAT2 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D007370:Interferon Type I; D012333:RNA, Messenger; D050795:STAT2 Transcription Factor; D053633:Receptor, Interferon alpha-beta