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Blank, T.* ; Detje, C.N.* ; Spieß, A.* ; Hagemeyer, N.* ; Brendecke, S.M.* ; Wolfart, J.* ; Staszewski, O.* ; Zöller, T.* ; Papageorgiou, I.* ; Schneider, J.* ; Paricio-Montesinos, R.* ; Eisel, U.L.* ; Manahan-Vaughan, D.* ; Jansen, S.* ; Lienenklaus, S.* ; Lu, B.* ; Imai, Y.* ; Müller, M.* ; Goelz, S.E.* ; Baker, D.P.* ; Schwaninger, M.* ; Kann, O.* ; Heikenwälder, M. ; Kalinke, U.* ; Prinz, M.*

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

Immunity 44, 901-912 (2016)
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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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Cxcl10 ; Cxcr3 ; Ifn ; Ifnar1 ; Ips-1 ; Mavs ; Behavior ; Brain ; Depression ; Endothelia ; Epithelia ; Influenza ; Neurons ; Signal Transduction ; Type I Interferon ; Virus Infection; Central-nervous-system; Double-stranded-rna; Long-term Potentiation; Synaptic Plasticity; Major Depression; In-vivo; Rig-i; Mice; Cells; Inflammation
Language english
Publication Year 2016
HGF-reported in Year 2016
ISSN (print) / ISBN 1074-7613
e-ISSN 1097-4180
Journal Immunity
Quellenangaben Volume: 44, Issue: 4, Pages: 901-912 Article Number: , Supplement: ,
Publisher Cell Press
Publishing Place Cambridge, Mass.
Reviewing status Peer reviewed
Institute(s) Institute of Virology (VIRO)
POF-Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Research field(s) Immune Response and Infection
PSP Element(s) G-551600-001
DOI 10.1016/j.immuni.2016.04.005
WOS ID WOS:000374444300020
PubMed ID 27096319
Erfassungsdatum 2016-05-12
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