Cutting edge: Inhibition of hepatitis B virus replication by activated NK T cells does not require inflammatory cell recruitment to the liver.
We have previously reported that intrahepatic NK T cells activated by alpha-galactosylceramide inhibit hepatitis B virus replication noncytopathically in the liver of transgenic mice. This effect is mediated by antiviral cytokines directly produced by activated NK T cells and/or by other cytokine-producing inflammatory cells that are recruited into the liver. In this study, we demonstrated that IFN-gamma produced by activated NK T cells induced parenchymal and nonparenchymal cells of the liver to produce high levels of CXC chemokine ligands 9 and 10, which mediated the intrahepatic recruitment of lymphomononuclear inflammatory cells. Recruitment of these cells was not necessary for the antiviral activity, indicating that direct activation of the intrahepatic resident NK T cell is sufficient to control viral replication in this model.
Kakimi
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K
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
Lane
T E
TE
Chisari
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FV
Guidotti
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LG
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000235:genetics / Q000502:physiology; D002634:Chemotaxis, Leukocyte; D005698:Galactosylceramidase / Q000494:pharmacology; D006509:Hepatitis B / Q000235:genetics / Q000276:immunology* / Q000821:virology; D006515:Hepatitis B virus / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma / Q000502:physiology; D007694:Killer Cells, Natural / Q000276:immunology*; D007700:Kinetics; D008099:Liver / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000096:biosynthesis; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014779:Virus Replication / Q000276:immunology*
D000998:Antiviral Agents; C080810:CXCL9 protein, human; C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; C515188:Cxcr3 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D007371:Interferon-gamma; D005698:Galactosylceramidase