Show simple item record

dc.contributor.authorLercher, Alexander
dc.contributor.authorBhattacharya, Anannya
dc.contributor.authorPopa, Alexandra M
dc.contributor.authorCaldera, Michael
dc.contributor.authorSchlapansky, Moritz F
dc.contributor.authorBaazim, Hatoon
dc.contributor.authorAgerer, Benedikt
dc.contributor.authorGürtl, Bettina
dc.contributor.authorKosack, Lindsay
dc.contributor.authorMájek, Peter
dc.contributor.authorBrunner, Julia S
dc.contributor.authorVitko, Dijana
dc.contributor.authorPinter, Theresa
dc.contributor.authorGenger, Jakob-Wendelin
dc.contributor.authorOrlova, Anna
dc.contributor.authorPikor, Natalia
dc.contributor.authorReil, Daniela
dc.contributor.authorOzsvár-Kozma, Maria
dc.contributor.authorKalinke, Ulrich
dc.contributor.authorLudewig, Burkhard
dc.contributor.authorMoriggl, Richard
dc.contributor.authorBennett, Keiryn L
dc.contributor.authorMenche, Jörg
dc.contributor.authorCheng, Paul N
dc.contributor.authorSchabbauer, Gernot
dc.contributor.authorTrauner, Michael
dc.contributor.authorKlavins, Kristaps
dc.contributor.authorBergthaler, Andreas
dc.date.accessioned2020-01-06T10:14:11Z
dc.date.available2020-01-06T10:14:11Z
dc.date.issued2019-12-17
dc.identifier.citationImmunity. 2019 Dec 17;51(6):1074-1087.e9. doi: 10.1016/j.immuni.2019.10.014. Epub 2019 Nov 26.en_US
dc.identifier.issn1097-4180
dc.identifier.pmid31784108
dc.identifier.doi10.1016/j.immuni.2019.10.014
dc.identifier.urihttp://hdl.handle.net/10033/622062
dc.description.abstractInfections induce complex host responses linked to antiviral defense, inflammation, and tissue damage and repair. We hypothesized that the liver, as a central metabolic hub, may orchestrate systemic metabolic changes during infection. We infected mice with chronic lymphocytic choriomeningitis virus (LCMV), performed RNA sequencing and proteomics of liver tissue, and integrated these data with serum metabolomics at different infection phases. Widespread reprogramming of liver metabolism occurred early after infection, correlating with type I interferon (IFN-I) responses. Viral infection induced metabolic alterations of the liver that depended on the interferon alpha/beta receptor (IFNAR1). Hepatocyte-intrinsic IFNAR1 repressed the transcription of metabolic genes, including Otc and Ass1, which encode urea cycle enzymes. This led to decreased arginine and increased ornithine concentrations in the circulation, resulting in suppressed virus-specific CD8+ T cell responses and ameliorated liver pathology. These findings establish IFN-I-induced modulation of hepatic metabolism and the urea cycle as an endogenous mechanism of immunoregulation. VIDEO ABSTRACT.en_US
dc.language.isoenen_US
dc.publisherElsevier/ Cel Pressen_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectCD8 T cellsen_US
dc.subjecthepatitisen_US
dc.subjecthepatocyteen_US
dc.subjectimmunometabolismen_US
dc.subjectinfectionen_US
dc.subjectinflammationen_US
dc.subjectinterferonsen_US
dc.subjectliveren_US
dc.subjecturea cycleen_US
dc.subjectvirusen_US
dc.titleType I Interferon Signaling Disrupts the Hepatic Urea Cycle and Alters Systemic Metabolism to Suppress T Cell Function.en_US
dc.typeArticleen_US
dc.contributor.departmentTWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany.en_US
dc.identifier.journalImmunityen_US
refterms.dateFOA2020-01-06T10:14:11Z
dc.source.journaltitleImmunity


Files in this item

Thumbnail
Name:
Publisher version
Thumbnail
Name:
Lercher et al.pdf
Size:
5.257Mb
Format:
PDF
Description:
Open Access article

This item appears in the following Collection(s)

Show simple item record

Attribution-NonCommercial-ShareAlike 4.0 International
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-ShareAlike 4.0 International