Liver Monocytes and Kupffer Cells Remain Transcriptionally Distinct during Chronic Viral Infection.
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 virus-induced chronic hepatitis.
Department of Gastroenterology and Hepatology Erasmus University Medical Center, Rotterdam, The Netherlands.
Martijn D B
MD
van de Garde
Department of Gastroenterology and Hepatology Erasmus University Medical Center, Rotterdam, The Netherlands.
Dowty
D
Movita
Department of Gastroenterology and Hepatology Erasmus University Medical Center, Rotterdam, The Netherlands.
Marieke
M
van der Heide
Janssen-Pharmaceutica NV, Beerse, Belgium.
Florence
F
Herschke
Janssen-Pharmaceutica NV, Beerse, Belgium.
Sandra
S
De Jonghe
Department of Molecular and Comparative Pathobiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
Lucio
L
Gama
Department of Gastroenterology and Hepatology Erasmus University Medical Center, Rotterdam, The Netherlands.
Andre
A
Boonstra
Department of Gastroenterology and Hepatology Erasmus University Medical Center, Rotterdam, The Netherlands.
Thomas
T
Vanwolleghem
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D005260:Female; D019694:Hepatitis B, Chronic / Q000235:genetics* / Q000276:immunology*; D007728:Kupffer Cells / Q000276:immunology / Q000378:metabolism*; D008099:Liver / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D010641:Phenotype; D014158:Transcription, Genetic
D000956:Antigens, Viral