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- Title
Hepatitis B virus-induced lipid alterations contribute to natural killer T cell-dependent protective immunity.
- Authors
Zeissig, Sebastian; Murata, Kazumoto; Sweet, Lindsay; Publicover, Jean; Hu, Zongyi; Kaser, Arthur; Bosse, Esther; Iqbal, Jahangir; Hussain, M Mahmood; Balschun, Katharina; Röcken, Christoph; Arlt, Alexander; Günther, Rainer; Hampe, Jochen; Schreiber, Stefan; Baron, Jody L; Moody, D Branch; Liang, T Jake; Blumberg, Richard S
- Abstract
In most adult humans, hepatitis B is a self-limiting disease leading to life-long protective immunity, which is the consequence of a robust adaptive immune response occurring weeks after hepatitis B virus (HBV) infection. Notably, HBV-specific T cells can be detected shortly after infection, but the mechanisms underlying this early immune priming and its consequences for subsequent control of viral replication are poorly understood. Using primary human and mouse hepatocytes and mouse models of transgenic and adenoviral HBV expression, we show that HBV-expressing hepatocytes produce endoplasmic reticulum (ER)-associated endogenous antigenic lipids including lysophospholipids that are generated by HBV-induced secretory phospholipases and that lead to activation of natural killer T (NKT) cells. The absence of NKT cells or CD1d or a defect in ER-associated transfer of lipids onto CD1d results in diminished HBV-specific T and B cell responses and delayed viral control in mice. NKT cells may therefore contribute to control of HBV infection through sensing of HBV-induced modified self-lipids.
- Subjects
HEPATITIS B virus; MICROBIAL lipids; HEPATITIS B -- Immunological aspects; KILLER cells; T cells; IMMUNITY; IMMUNE response; VIRAL replication
- Publication
Nature Medicine, 2012, Vol 18, Issue 7, p1060
- ISSN
1078-8956
- Publication type
Article
- DOI
10.1038/nm.2811