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dc.contributor.authorBorst, Katharina
dc.contributor.authorFrenz, Theresa
dc.contributor.authorSpanier, Julia
dc.contributor.authorTegtmeyer, Pia-Katharina
dc.contributor.authorChhatbar, Chintan
dc.contributor.authorSkerra, Jennifer
dc.contributor.authorGhita, Luca
dc.contributor.authorNamineni, Sukumar
dc.contributor.authorLienenklaus, Stefan
dc.contributor.authorKöster, Mario
dc.contributor.authorHeikenwaelder, Mathias
dc.contributor.authorSutter, Gerd
dc.contributor.authorKalinke, Ulrich
dc.date.accessioned2018-07-31T12:49:10Z
dc.date.available2018-07-31T12:49:10Z
dc.date.issued2017-12-21
dc.identifier.issn1600-0641
dc.identifier.pmid29274730
dc.identifier.doi10.1016/j.jhep.2017.11.029
dc.identifier.urihttp://hdl.handle.net/10033/621432
dc.description.abstractVirus-induced fulminant hepatitis is a major cause of acute liver failure. During acute viral hepatitis the impact of type I interferon (IFN-I) on myeloid cells, including liver-resident Kupffer cells (KC), is only partially understood. Herein, we dissected the impact of locally induced IFN-I responses on myeloid cell function and hepatocytes during acute liver inflammation. Two different DNA-encoded viruses, vaccinia virus (VACV) and murine cytomegalovirus (MCMV), were studied. In vivo imaging was applied to visualize local IFN-β induction and IFN-I receptor (IFNAR) triggering in VACV-infected reporter mice. Furthermore, mice with a cell type-selective IFNAR ablation were analyzed to dissect the role of IFNAR signaling in myeloid cells and hepatocytes. Experiments with Cx3cr1 VACV infection induced local IFN-β responses, which lead to IFNAR signaling primarily within the liver. IFNAR triggering was needed to control the infection and prevent fulminant hepatitis. The severity of liver inflammation was independent of IFNAR triggering of hepatocytes, whereas IFNAR triggering of myeloid cells protected from excessive inflammation. Upon VACV or MCMV infection KC disappeared, whereas infiltrating monocytes differentiated to KC afterwards. During IFNAR triggering such replenished monocyte-derived KC comprised more IFNAR-deficient than -competent cells in mixed bone marrow chimeric mice, whereas after the decline of IFNAR triggering both subsets showed an even distribution. Upon VACV infection IFNAR triggering of myeloid cells, but not of hepatocytes, critically modulates acute viral hepatitis. During infection with DNA-encoded viruses IFNAR triggering of liver-infiltrating blood monocytes delays the development of monocyte-derived KC, pointing towards new therapeutic strategies for acute viral hepatitis.en_US
dc.rightsAttribution-NonCommercial-ShareAlike 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/us/*
dc.subjectDNA virus infectionen_US
dc.subjectInnate immunityen_US
dc.subjectLiver inflammationen_US
dc.subjectMonocyte infiltrationen_US
dc.titleType I interferon receptor signaling delays Kupffer cell replenishment during acute fulminant viral hepatitis.en_US
dc.typeArticleen_US
dc.contributor.departmentTWINCORE, Zentrum für experimentelle und klinischeInfektionsforschung GmbH, Feodor-Lynen-Str. 7, 30625 Hannover, Germany.en_US
dc.source.journaltitleJournal of hepatology


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