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Publikation: Zeitschriftenartikel
Brain endothelial- and epithelial-specific interferon receptor chain 1 drives virus-induced sickness behavior and cognitive impairment
Grunddaten
Abstract
Autoren
Grunddaten
Titel
Brain endothelial- and epithelial-specific interferon receptor chain 1 drives virus-induced sickness behavior and cognitive impairment
Veröffentlicht in
Immunity. - [Cambridge, Mass.] : Cell Press
Erscheinungsjahr
2016
Seiten (von – bis)
901 – 912
Band
44
Heft-Nr.
4
Jahr
2016
Publikationsform
Elektronische Ressource
Publikationsart
Zeitschriftenartikel
Sprache
Englisch
DOI
10.1016/j.immuni.2016.04.005
Letzte Änderung
28.03.2017 16:14:02
Bearbeitungsstatus
durch UB Rostock abschließend validiert
Dauerhafte URL
http://purl.uni-rostock.de/fodb/pub/51835
Links zu Katalogen
Abstract
Sickness behavior and cognitive dysfunction occur frequently by unknown mechanisms in virus-infected individuals with malignancies treated with type I interferons (IFNs) and in patients with autoimmune disorders. We found that during sickness behavior, single-stranded RNA viruses, double-stranded RNA ligands, and IFNs shared pathways involving engagement of melanoma differentiation-associated protein 5 (MDA5), retinoic acid-inducible gene 1 (RIG-I), and mitochondrial antiviral signaling protein (MAVS), and subsequently induced IFN responses specifically in brain endothelia and epithelia of mice. Behavioral alterations were specifically dependent on brain endothelial and epithelial IFN receptor chain 1 (IFNAR). Using gene profiling, we identified that the endothelia-derived chemokine ligand CXCL10 mediated behavioral changes through impairment of synaptic plasticity. These results identified brain endothelial and epithelial cells as natural gatekeepers for virus-induced sickness behavior, demonstrated tissue specific IFNAR engagement, and established the CXCL10-CXCR3 axis as target for the treatment of behavioral changes during virus infection and type I IFN therapy.
Autoren
Blank, Thomas
Detje, Claudia Nadine
Spieß, Alena
Wolfart, Jakob
Papageorgiou, Ismini E.
Schneider, Justus
Kann, Oliver