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Publikation: Zeitschriftenartikel

Brain endothelial- and epithelial-specific interferon receptor chain 1 drives virus-induced sickness behavior and cognitive impairment


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 Diese Publikation in der Universitätsbibliographie Diese Publikation im GBV-Katalog

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