Hepatitis B virus–induced lipid alterations contribute to natural killer T cell–dependent protective immunity

Autor: Zongyi Hu, Esther Bosse, Stefan Schreiber, Rainer Günther, Jochen Hampe, Christoph Röcken, Alexander Arlt, M. Mahmood Hussain, Jody L. Baron, Richard S. Blumberg, Jahangir Iqbal, Jean Publicover, Arthur Kaser, Kazumoto Murata, D. Branch Moody, T. Jake Liang, Katharina Balschun, Sebastian Zeissig, Lindsay Sweet
Rok vydání: 2012
Předmět:
Hepatitis B virus
Priming (immunology)
chemical and pharmacologic phenomena
Adaptive Immunity
Lymphocyte Activation
medicine.disease_cause
Article
General Biochemistry
Genetics and Molecular Biology
Adenoviridae
Interferon-gamma
Mice
03 medical and health sciences
Hepatitis B
Chronic
0302 clinical medicine
Immune system
Antigen
medicine
Animals
Humans
Phospholipases A2
Secretory
B cell
030304 developmental biology
0303 health sciences
Hepatitis B Surface Antigens
biology
Immunity
virus diseases
General Medicine
Lipid Metabolism
Acquired immune system
Natural killer T cell
Virology
Coculture Techniques
digestive system diseases
3. Good health
medicine.anatomical_structure
CD1D
Immunology
Hepatocytes
biology.protein
Natural Killer T-Cells
Antigens
CD1d
Lysophospholipids
Carrier Proteins
Lysosomes
Biomarkers
030215 immunology
Zdroj: Nature Medicine. 18:1060-1068
ISSN: 1546-170X
1078-8956
Popis: 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.
Databáze: OpenAIRE
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