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

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Sebastian Zeissig - , Chair of Mucosal Immunology, Division of Gastroenterology, Brigham and Women's Hospital, Harvard Medical School (HMS) (Author)
  • Kazumoto Murata - (Author)
  • Lindsay Sweet - (Author)
  • Jean Publicover - (Author)
  • Zongyi Hu - (Author)
  • Arthur Kaser - (Author)
  • Esther Bosse - (Author)
  • Jahangir Iqbal - (Author)
  • M Mahmood Hussain - (Author)
  • Katharina Balschun - (Author)
  • Christoph Röcken - (Author)
  • Alexander Arlt - (Author)
  • Rainer Günther - (Author)
  • Jochen Hampe - , Department of internal Medicine I (Author)
  • Stefan Schreiber - (Author)
  • Jody L Baron - (Author)
  • D Branch Moody - (Author)
  • T Jake Liang - (Author)
  • Richard S Blumberg - (Author)

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.

Details

Original languageEnglish
Pages (from-to)1060-8
Number of pages9
JournalNature medicine
Volume18
Issue number7
Publication statusPublished - Jul 2012
Peer-reviewedYes

External IDs

PubMedCentral PMC3478098
Scopus 84863707404

Keywords

Sustainable Development Goals

Keywords

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