Inhibition of HIV-1 transmission in trans from dendritic cells to CD4+T lymphocytes by natural antibodies to the CRD domain of DC-SIGN purified from breast milk and intravenous immunoglobulins
| Autor: | Gérard Grésenguet, Laurent Bélec, Michel D. Kazatchkine, Nadine Nasreddine, Sylvie Aubry, Hakim Hocini, Mary Requena, Jean-Chrysostome Gody, Héla Saïdi, Hicham Bouhlal, Rafick-Pierre Sekaly |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
CD4-Positive T-Lymphocytes
Immunoglobulin A Immunology Virus Attachment HIV Infections Receptors Cell Surface Peptide Virus HeLa Humans Immunology and Allergy Lectins C-Type chemistry.chemical_classification Innate immune system Milk Human biology Immunoglobulins Intravenous Dendritic Cells Original Articles biology.organism_classification Virology Molecular biology Immunity Innate DC-SIGN chemistry Polyclonal antibodies Immunoglobulin G HIV-1 biology.protein Antibody Cell Adhesion Molecules HeLa Cells |
| Zdroj: | Immunology. 123:508-518 |
| ISSN: | 1365-2567 0019-2805 |
| DOI: | 10.1111/j.1365-2567.2007.02717.x |
| Popis: | The present study demonstrates that human breast milk and normal human polyclonal immunoglobulins purified from plasma [intravenous immunoglobulins (IVIg)] contain functional natural immunoglobulin A (IgA) and IgG antibodies directed against the carbohydrate recognition domain (CRD) domain of the dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) molecule, which is involved in the binding of human immunodeficiency virus (HIV)-1 to dendritic cells (DCs). Antibodies to DC-SIGN CRD were affinity-purified on a matrix to which a synthetic peptide corresponding to the N-terminal CRD domain (amino-acid 342-amino-acid 371) had been coupled. The affinity-purified antibodies bound to the DC-SIGN peptide and to the native DC-SIGN molecule expressed by HeLa DC-SIGN+ cells and immature monocyte-derived dendritic cells (iMDDCs), in a specific and dose-dependent manner. At an optimal dose of 200 microg/ml, natural antibodies to DC-SIGN CRD peptide purified from breast milk and IVIg stained 25 and 20% of HeLa DC-SIGN+ cells and 32 and 12% of iMDDCs, respectively. Anti-DC-SIGN CRD peptide antibodies inhibited the attachment of virus to HeLa DC-SIGN by up to 78% and the attachment to iMDDCs by only 20%. Both breast milk- and IVIg-derived natural antibodies to the CRD peptide inhibited 60% of the transmission in trans of HIV-1(JRCSF), an R5-tropic strain, from iMDDCs to CD4+ T lymphocytes. Taken together, these observations suggest that the attachment of HIV to DCs and transmission in trans to autologous CD4+ T lymphocytes occur through two independent mechanisms. Our data support a role of natural antibodies to DC-SIGN in the modulation of postnatal HIV transmission through breast-feeding and in the natural host defence against HIV-1 in infected individuals. |
| Databáze: | OpenAIRE |
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