The impact of nanoparticle ligand density on dendritic-cell targeted vaccines
| Autor: | Arunima Bandyopadhyay, Stacey L. Demento, Linda K. Bockenstedt, Rebecca L. Fine, Tarek M. Fahmy |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
CD36
T-Lymphocytes Biophysics Bioengineering Receptors Cell Surface Article Biomaterials Minor Histocompatibility Antigens Mice Antigen C-type lectin Antigens CD parasitic diseases Minor histocompatibility antigen Animals Lectins C-Type Scavenger receptor Receptor Vaccines Microscopy Confocal biology Dendritic cell Dendritic Cells Flow Cytometry Molecular biology Cell biology Interleukin-10 Mice Inbred C57BL Interleukin 10 Mechanics of Materials Ceramics and Composites biology.protein Cytokines Nanoparticles |
| Popis: | Dendritic-cell (DC) targeted antigen delivery systems hold promise for enhancing vaccine efficacy and delivery of therapeutics. However, it is not known how the number and density of targeting ligands on such systems may affect DC function and subsequent T cell response. We modified the surface of biodegradable nanoparticles loaded with antigen with different densities of the mAb to the DC lectin DEC-205 receptor and assessed changes in the cytokine response of DCs and T cells. DEC-205 targeted nanoparticles unexpectedly induced a differential cytokine response that depended on the density of ligands on the surface. Strikingly, nanoparticle surface density of DEC-205 mAb increased the amount of anti-inflammatory, IL-10, produced by DCs and T cells. Boosting mice with DEC-205 targeted OVA-nanoparticles after immunization with an antigen in CFA induced a similar pattern of IL-10 response. The correlation between DC production of IL-10 as a function of the density of anti-DEC-205 is shown to be due to cross-linking of the DEC-205 receptor. Cross-linking also increased DC expression of the scavenger receptor CD36, and blockade of CD36 largely abrogated the IL-10 response. Our studies highlight the importance of target ligand density in the design of vaccine delivery systems. |
| Databáze: | OpenAIRE |
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