title: Homeostatic interferon expression in neurons is sufficient for early control of viral infection.
abstract: The mechanisms by which neurons respond to inflammatory mediators such as interferons (IFNs) remain largely undefined. We previously showed that the activation and nuclear localization of the core IFN signaling molecule, Stat1, are muted and delayed in primary mouse hippocampal neurons treated with IFN gamma as compared to control mouse embryonic fibroblasts (MEFs). Here, we show that the kinetics of Stat1 and Stat2 activation following type I IFN exposure are also unique in neurons, affecting gene expression and neuronal response. Specifically, despite lower basal expression of many IFN stimulated genes in neurons, basal expression of the type I IFN themselves is significantly higher in primary hippocampal neurons compared to MEF. Elevated homeostatic IFN in neurons is critical and sufficient for early control of viral infection. These data provide further evidence that neurons exploit unique signaling responses to IFNs, and define an important contribution of homeostatic IFN within the CNS. Such differences are likely critical for the ability of neurons to survive a viral challenge.
authors: Fox Chase Cancer Center, Program in Immune Cell Development and Host Defense, 333 Cottman Avenue, Philadelphia, PA 19111, United States; Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19129, United States.
authors: Sarah E
authors: SE
authors: Cavanaugh
authors: Fox Chase Cancer Center, Program in Immune Cell Development and Host Defense, 333 Cottman Avenue, Philadelphia, PA 19111, United States; Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19129, United States.
authors: Alicia M
authors: AM
authors: Holmgren
authors: Fox Chase Cancer Center, Program in Immune Cell Development and Host Defense, 333 Cottman Avenue, Philadelphia, PA 19111, United States. Electronic address: glenn.rall@fccc.edu.
authors: Glenn F
authors: GF
authors: Rall
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D007372:Interferons / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D008457:Measles / Q000378:metabolism* / Q000473:pathology; D008459:Measles virus / Q000472:pathogenicity*; D051916:Membrane Cofactor Protein / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000821:virology; D010751:Phosphopyruvate Hydratase / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000378:metabolism; D050795:STAT2 Transcription Factor / Q000378:metabolism; D013997:Time Factors; D014452:Ubiquitins / Q000235:genetics / Q000378:metabolism
chemical_list: D016207:Cytokines; C489550:G1p2 protein, mouse; D051916:Membrane Cofactor Protein; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; D014452:Ubiquitins; D007372:Interferons; D015088:2',5'-Oligoadenylate Synthetase; D010751:Phosphopyruvate Hydratase
keywords: Interferon; Neuron; Signaling; Stat1; Stat2