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Assessing the Innate Sensing of HIV-1 Infected CD4+ T Cells by Plasmacytoid Dendritic Cells Using an Ex vivo Co-culture System.
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Plasmacytoid dendritic cells sense hepatitis C virus-infected cells, produce interferon, and inhibit infection

Ken Takahashi1, Shinichi Asabe, Stefan Wieland

  • 1Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.

Proceedings of the National Academy of Sciences of the United States of America
|March 17, 2010
PubMed

Insights

Hepatitis C virus (HCV) activates immune cells called plasmacytoid dendritic cells (pDCs) through cell-to-cell contact, prompting them to produce a strong interferon response that inhibits viral replication.

Area of Science:

  • Virology
  • Immunology
  • Hepatology

Background:

  • Hepatitis C virus (HCV) infects over 170 million people globally, causing liver disease.
  • HCV establishes chronic infection by evading the host's innate immune system.
  • The precise mechanism of interferon (IFN) induction in HCV-infected livers remains unclear.

Purpose of the Study:

  • To investigate how Hepatitis C virus (HCV) induces a type 1 interferon (IFN) response in the liver.
  • To identify the cellular players and mechanisms involved in HCV-mediated IFN production.

Main Methods:

  • Utilized in vitro cell culture models with HCV-infected cells and plasmacytoid dendritic cells (pDCs).
  • Investigated the role of viral replication, cell-cell contact, and Toll-like receptor 7 (TLR7) signaling.
  • Assessed the antiviral activity of pDC-conditioned media on HCV infection.

Main Results:

  • HCV-infected cells induce a robust IFN response in pDCs, requiring active viral replication and cell-cell contact.
  • Toll-like receptor 7 (TLR7) signaling in pDCs is crucial for this IFN induction.
  • Activated pDC supernatant inhibits HCV infection in an IFN receptor-dependent manner.
  • HCV subgenomic replicons, but not free virus particles, trigger this pDC activation, suggesting cell-to-cell RNA transfer.

Conclusions:

  • HCV-infected cells activate pDCs to produce IFN via a novel cell-cell RNA transfer mechanism, bypassing direct infection of pDCs.
  • This process explains in vivo IFN induction in the liver during HCV infection.
  • Reveals a new aspect of innate immune response where viruses can subvert host defenses through non-infectious cell-to-cell interactions.

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