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Dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin mediates binding and internalization

Diego Serrano-Gómez1, Angeles Domínguez-Soto, Julio Ancochea

  • 1Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Cientificas, Madrid, Spain.

Journal of Immunology (Baltimore, Md. : 1950)
|October 21, 2004
PubMed

Insights

Dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN) binds Aspergillus fumigatus conidia. This interaction is crucial for fungal infection and spreading in immunocompromised patients.

Area of Science:

  • Mycology
  • Immunology
  • Infectious Diseases

Background:

  • Aspergillus fumigatus causes life-threatening opportunistic infections in immunocompromised individuals.
  • Dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN) is a lectin receptor involved in pathogen recognition by dendritic cells.
  • DC-SIGN facilitates viral and bacterial entry into human dendritic cells.

Purpose of the Study:

  • To investigate the interaction between DC-SIGN and Aspergillus fumigatus.
  • To determine the role of DC-SIGN in the pathogenesis of invasive aspergillosis.

Main Methods:

  • Demonstration of DC-SIGN-dependent binding of A. fumigatus conidia to transfectants and monocyte-derived dendritic cells.
  • Inhibition studies using anti-DC-SIGN antibodies.
  • Analysis of A. fumigatus galactomannans' effect on binding.
  • Assessment of DC-SIGN expression in lung dendritic cells and alveolar macrophages.

Main Results:

  • DC-SIGN specifically interacts with clinical isolates of A. fumigatus.
  • DC-SIGN-dependent binding and internalization of A. fumigatus conidia were observed.
  • Binding was inhibited by anti-DC-SIGN antibodies and abolished by fungal galactomannans.
  • DC-SIGN was found in lung dendritic cells and alveolar macrophages, mediating fungal attachment.

Conclusions:

  • DC-SIGN plays a significant role in the initial adherence of A. fumigatus conidia to host cells.
  • The interaction suggests DC-SIGN involvement in pulmonary infection and fungal dissemination in invasive aspergillosis.

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