Microdomains of the C-type lectin DC-SIGN are portals for virus entry into dendritic cells

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An Efficient and High Yield Method for Isolation of Mouse Dendritic Cell Subsets
09:09

An Efficient and High Yield Method for Isolation of Mouse Dendritic Cell Subsets

Published on: April 18, 2016

Alessandra Cambi1, Frank de Lange, Noortje M van Maarseveen

  • 1Dept. of Tumor Immunology, Nijmegen Center for Molecular Life Sciences, University Medical Center Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, Netherlands.

The Journal of Cell Biology
|January 8, 2004
PubMed

Insights

Dendritic cell-specific intercellular adhesion molecule grabbing non-integrin (DC-SIGN) organizes into microdomains on the cell membrane. This organization is crucial for binding and internalizing viruses like HIV-1, highlighting its role in pathogen entry.

Area of Science:

  • Immunology
  • Cell Biology
  • Virology

Background:

  • Dendritic cell-specific intercellular adhesion molecule grabbing non-integrin (DC-SIGN) is a C-type lectin receptor on dendritic cells.
  • DC-SIGN mediates the binding and internalization of various viruses, including HIV-1, but its precise mechanism as a phagocytic receptor is unclear.

Purpose of the Study:

  • To investigate the relationship between DC-SIGN's function as a viral receptor and its localization on the plasma membrane.
  • To elucidate the structural organization of DC-SIGN and its role in viral particle binding and uptake.

Main Methods:

  • High-resolution electron microscopy to visualize DC-SIGN organization.
  • Biochemical experiments and confocal microscopy to determine DC-SIGN's association with lipid rafts.
  • Functional assays to assess the impact of DC-SIGN microdomain organization on viral binding and internalization.

Main Results:

  • DC-SIGN forms well-defined microdomains (average 200 nm diameter) on the plasma membrane of human monocyte-derived DCs.
  • These DC-SIGN microdomains are localized within lipid rafts.
  • The organization of DC-SIGN into microdomains is essential for efficient binding and internalization of virus particles.

Conclusions:

  • DC-SIGN's functional role as a viral receptor is directly linked to its microlocalization and organization into membrane microdomains.
  • These DC-SIGN-rich microdomains act as critical docking sites for pathogens like HIV-1, facilitating host cell entry.
  • Understanding DC-SIGN microdomain organization provides insights into viral pathogenesis and potential therapeutic targets.

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