The DC-SIGN-CD56 interaction inhibits the anti-dendritic cell cytotoxicity of CD56 expressing cells.

Alexey A Nabatov,Ivan S Raginov

doi:10.1186/s13027-015-0043-8

Abstract

BackgroundThis study aimed to clarify interactions of the pattern-recognition receptor DC-SIGN with cells from the HIV-infected peripheral blood lymphocyte cultures.MethodsCells 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.ResultsIn 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 CD56pos cells. The treatment of CD56pos cells with a peptide, blocking the weakly polysialylated CD56-specifc trans-homophilic interactions, inhibited their anti-dendritic cells cytotoxicity.ConclusionsThe interaction between DC-SIGN and CD56 inhibits homotypic intercellular interactions of CD56pos cells and protects DC-SIGN expressing dendritic cells against CD56pos 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.

Highlights

This study aimed to clarify interactions of the pattern-recognition receptor dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) with cells from the HIV-infected peripheral blood lymphocyte cultures
dendritic cells (DCs)-SIGN rarely binds to human immunodeficiency virus type 1 (HIV-1) infected cells To study the interactions between HIV-1 infected cells and DC-SIGN, donor peripheral blood lymphocytes (PBLs) were activated, infected with HIV-1 and stained with a soluble DC-SIGN-Fc chimera
When the rare donors infected cells were stained for CD4, an additional population of DC-SIGNLposCD4pos cells was detected (Fig. 1c)

Summary

Introduction

This study aimed to clarify interactions of the pattern-recognition receptor DC-SIGN with cells from the HIV-infected peripheral blood lymphocyte cultures. A state of unresponsiveness of the immune system to specific immunogens, can be reached by different mechanisms, including the dysregulation of dendritic cells (DCs). DCs play a central role in effective immune response development. Complete dysregulation or depletion of DCs causes immunodeficiency. Different stages of HIV and SIV infections vary in the level of DC dysregulation, the depletion of DCs from blood stream and from lymph nodes is characteristic for late stages of these infections [1,2,3,4]. The DC functional deficiency can be the key element for AIDS development.

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