Inflammatory monocytes recruited to the liver within 24 hours after virus-induced inflammation resemble kupffer cells but are functionally distinct

Dowty Movita, Martijn D B van de Garde, Paula Biesta, Kim Kreefft, Bart Haagmans, Elina Zuniga, Florence Herschke, Sandra De Jonghe, Harry L A Janssen, Lucio Gama, Andre Boonstra, Thomas Vanwolleghem

Research output: Contribution to journalArticle

Abstract

Due to a scarcity of immunocompetent animal models for viral hepatitis, little is known about the early innate immune responses in the liver. In various hepatotoxic models, both pro- and anti-inflammatory activities of recruited monocytes have been described. In this study, we compared the effect of liver inflammation induced by the Toll-like receptor 4 ligand lipopolysaccharide (LPS) with that of a persistent virus, lymphocytic choriomeningitis virus (LCMV) clone 13, on early innate intrahepatic immune responses in mice. LCMV infection induces a remarkable influx of inflammatory monocytes in the liver within 24 h, accompanied by increased transcript levels of several proinflammatory cytokines and chemokines in whole liver. Importantly, while a single LPS injection results in similar recruitment of inflammatory monocytes to the liver, the functional properties of the infiltrating cells are dramatically different in response to LPS versus LCMV infection. In fact, intrahepatic inflammatory monocytes are skewed toward a secretory phenotype with impaired phagocytosis in LCMV-induced liver inflammation but exhibit increased endocytic capacity after LPS challenge. In contrast, F4/80high-Kupffer cells retain their steady-state endocytic functions upon LCMV infection. Strikingly, the gene expression levels of inflammatory monocytes dramatically change upon LCMV exposure and resemble those of Kupffer cells. Since inflammatory monocytes outnumber Kupffer cells 24 h after LCMV infection, it is highly likely that inflammatory monocytes contribute to the intrahepatic inflammatory response during the early phase of infection. Our findings are instrumental in understanding the early immunological events during virus-induced liver disease and point toward inflammatory monocytes as potential target cells for future treatment options in viral hepatitis.

Original languageEnglish (US)
Pages (from-to)4809-4817
Number of pages9
JournalJournal of Virology
Volume89
Issue number9
DOIs
StatePublished - 2015

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Lymphocytic choriomeningitis virus
Kupffer cells
Kupffer Cells
monocytes
Monocytes
inflammation
Viruses
Inflammation
viruses
liver
Liver
Virus Diseases
lipopolysaccharides
Lipopolysaccharides
viral hepatitis
infection
Innate Immunity
Hepatitis
Toll-Like Receptor 4
liver diseases

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Movita, D., van de Garde, M. D. B., Biesta, P., Kreefft, K., Haagmans, B., Zuniga, E., ... Vanwolleghem, T. (2015). Inflammatory monocytes recruited to the liver within 24 hours after virus-induced inflammation resemble kupffer cells but are functionally distinct. Journal of Virology, 89(9), 4809-4817. https://doi.org/10.1128/JVI.03733-14

Inflammatory monocytes recruited to the liver within 24 hours after virus-induced inflammation resemble kupffer cells but are functionally distinct. / Movita, Dowty; van de Garde, Martijn D B; Biesta, Paula; Kreefft, Kim; Haagmans, Bart; Zuniga, Elina; Herschke, Florence; De Jonghe, Sandra; Janssen, Harry L A; Gama, Lucio; Boonstra, Andre; Vanwolleghem, Thomas.

In: Journal of Virology, Vol. 89, No. 9, 2015, p. 4809-4817.

Research output: Contribution to journalArticle

Movita, D, van de Garde, MDB, Biesta, P, Kreefft, K, Haagmans, B, Zuniga, E, Herschke, F, De Jonghe, S, Janssen, HLA, Gama, L, Boonstra, A & Vanwolleghem, T 2015, 'Inflammatory monocytes recruited to the liver within 24 hours after virus-induced inflammation resemble kupffer cells but are functionally distinct', Journal of Virology, vol. 89, no. 9, pp. 4809-4817. https://doi.org/10.1128/JVI.03733-14
Movita, Dowty ; van de Garde, Martijn D B ; Biesta, Paula ; Kreefft, Kim ; Haagmans, Bart ; Zuniga, Elina ; Herschke, Florence ; De Jonghe, Sandra ; Janssen, Harry L A ; Gama, Lucio ; Boonstra, Andre ; Vanwolleghem, Thomas. / Inflammatory monocytes recruited to the liver within 24 hours after virus-induced inflammation resemble kupffer cells but are functionally distinct. In: Journal of Virology. 2015 ; Vol. 89, No. 9. pp. 4809-4817.
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AU - Haagmans, Bart

AU - Zuniga, Elina

AU - Herschke, Florence

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