Liver monocytes and kupffer cells remain transcriptionally distinct during chronic viral infection

Martijn D B Van De Garde, Dowty Movita, Marieke Van Der Heide, Florence Herschke, Sandra De Jonghe, Lucio Gama, Andre Boonstra, Thomas Vanwolleghem

Research output: Contribution to journalArticle

Abstract

Due to the scarcity of immunocompetent animal models for chronic viral hepatitis, little is known about the role of the innate intrahepatic immune system during viral replication in the liver. These insights are however fundamental for the understanding of the inappropriate adaptive immune responses during the chronic phase of the infection. We apply the Lymphocytic Choriomenigitis Virus (LCMV) clone 13 mouse model to examine chronic virus-host interactions of Kupffer cells (KC) and infiltrating monocytes (IM) in an infected liver. LCMV infection induced overt clinical hepatitis, with rise in ALT and serum cytokines, and increased intrahepatic F4/80 expression. Despite ongoing viral replication, whole liver transcriptome showed baseline expression levels of inflammatory cytokines, interferons, and interferon induced genes during the chronic infection phase. Transcriptome analyses of sorted KC and IMs using NanoString technology revealed two unique phenotypes with only minimal overlap. At the chronic viral infection phase, KC showed no increased transcription of activation markers Cd80 and Cd86, but an increased expression of genes related to antigen presentation, whereas monocytes were more activated and expressed higher levels of TNF transcripts. Although both KCs and intrahepatic IM share the surface markers F4/80 and CD11b, their transcriptomes point towards distinctive roles during virusinduced chronic hepatitis.

Original languageEnglish (US)
Article numbere0166094
JournalPLoS One
Volume11
Issue number11
DOIs
Publication statusPublished - Nov 1 2016

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ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Van De Garde, M. D. B., Movita, D., Van Der Heide, M., Herschke, F., De Jonghe, S., Gama, L., ... Vanwolleghem, T. (2016). Liver monocytes and kupffer cells remain transcriptionally distinct during chronic viral infection. PLoS One, 11(11), [e0166094]. https://doi.org/10.1371/journal.pone.0166094