lysophosphatidylethanolamine and Hepatitis-B--Chronic

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.

Topics: Adaptive Immunity; Adenoviridae; Animals; Antigens, CD1d; Biomarkers; Carrier Proteins; Coculture Techniques; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis B, Chronic; Hepatocytes; Humans; Immunity; Interferon-gamma; Lipid Metabolism; Lymphocyte Activation; Lysophospholipids; Lysosomes; Mice; Natural Killer T-Cells; Phospholipases A2, Secretory

The study was carried out for the purpose of determining the diagnostic criteria applicable to the cirrhotic stage of chronic viral B-hepatitis (CVBH) by using the data of the phosphor-lipid spectrum of the blood serum. The phosphor-lipid spectrum of the blood serum was examined in 70 patients with CVBH and in 20 patients with small-nodular hepatic cirrhosis. Reliably lower contents of lysophosphatidyl serine (LPS), of lysophosphatidyl ethanolamine (LFE) and of phosphatidyl ethanolamine (PE) were found in patients with CVBH at the cirrhotic stage as compared to patients with CVBH, who did and did not abuse the alcohol. However, the latters had a higher level of the relative content of phosphatidyl choline (PC) as compared to the controls.

Topics: Alcoholism; Diagnosis, Differential; Hepatitis B, Chronic; Humans; Liver Cirrhosis; Lysophospholipids; Male; Phosphatidylcholines; Phosphatidylserines; Phospholipids