The DC-SIGN-CD56 interaction inhibits the anti-dendritic cell cytotoxicity of CD56 expressing cells
Alexey A Nabatov1, Ivan S Raginov2
1Science Center, Volga Region State Academy of Physical Culture, Sport and Tourism, 33, Universiade Village, Kazan, 420138 Russia ; Department of Molecular Cell Biology & Immunology, VU University Medical Center, Amsterdam, The Netherlands.
Background:
This study aimed to clarify interactions of the pattern-recognition receptor DC-SIGN with cells from the HIV-infected peripheral blood lymphocyte cultures.
Methods:
Cells from control and HIV-infected peripheral blood lymphocyte cultures were tested for the surface expression of DC-SIGN ligands. The DC-SIGN ligand expressing cells were analyzed for the role of DC-SIGN-ligand interaction in their functionality.
Results:
In the vast majority of experiments HIV-infected lymphocytes did not express detectable DC-SIGN ligands on their cell surfaces. In contrast, non-infected cells, carrying NK-specific marker CD56, expressed cell surface DC-SIGN ligands. The weakly polysialylated CD56 was identified as a novel DC-SIGN ligand. The treatment of DC-SIGN expressing dendritic cells with anti-DC-SIGN antibodies increased the anti-dendritic cell cytotoxicity of CD56(pos) cells. The treatment of CD56(pos) cells with a peptide, blocking the weakly polysialylated CD56-specifc trans-homophilic interactions, inhibited their anti-dendritic cells cytotoxicity.
Conclusions:
The interaction between DC-SIGN and CD56 inhibits homotypic intercellular interactions of CD56(pos) cells and protects DC-SIGN expressing dendritic cells against CD56(pos) cell-mediated cytotoxicity. This finding can have an impact on the development of approaches to HIV infection and cancer therapy as well as in transplantation medicine.
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