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by Keyword: Dendritic cells


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De Koker, Stefaan, Cui, Jiwei, Vanparijs, Nane, Albertazzi, Lorenzo, Grooten, Johan, Caruso, Frank, De Geest, Bruno G., (2016). Engineering polymer hydrogel nanoparticles for lymph node-targeted delivery Angewandte Chemie - International Edition , 55, (4), 1334-1339

The induction of antigen-specific adaptive immunity exclusively occurs in lymphoid organs. As a consequence, the efficacy by which vaccines reach these tissues strongly affects the efficacy of the vaccine. Here, we report the design of polymer hydrogel nanoparticles that efficiently target multiple immune cell subsets in the draining lymph nodes. Nanoparticles are fabricated by infiltrating mesoporous silica particles (ca. 200 nm) with poly(methacrylic acid) followed by disulfide-based crosslinking and template removal. PEGylation of these nanoparticles does not affect their cellular association in vitro, but dramatically improves their lymphatic drainage in vivo. The functional relevance of these observations is further illustrated by the increased priming of antigen-specific T cells. Our findings highlight the potential of engineered hydrogel nanoparticles for the lymphatic delivery of antigens and immune-modulating compounds.

Keywords: Dendritic cells, Disulfides, Hydrogels, Nanoparticles, Vaccines


Izquierdo-Useros, Nuria, Esteban, Olga, Rodriguez-Plata, Maria T., Erkizia, Itziar, Prado, Julia G., Blanco, Julia, Garcia-Parajo, Maria F., Martinez-Picado, Javier, (2011). Dynamic imaging of cell-free and cell-associated viral capture in mature dendritic cells Traffic , 12, (12), 1702-1713

Dendritic cells (DCs) capture human immunodeficiency virus (HIV) through a non-fusogenic mechanism that enables viral transmission to CD4(+) T cells, contributing to in vivo viral dissemination. Although previous studies have provided important clues to cell-free viral capture by mature DCs (mDCs), dynamic and kinetic insight on this process is still missing. Here, we used three-dimensional videomicroscopy and single-particle tracking approaches to dynamically dissect both cell-free and cell-associated viral capture by living mDCs. We show that cell-free virus capture by mDCs operates through three sequential phases: virus binding through specific determinants expressed in the viral particle, polarized or directional movements toward concrete regions of the cell membrane and virus accumulation in a sac-like structure where trapped viral particles display a hindered diffusive behavior. Moreover, real-time imaging of cell-associated viral transfer to mDCs showed a similar dynamics to that exhibited by cell-free virus endocytosis leading to viral accumulation in compartments. However, cell-associated HIV type 1 transfer to mDCs was the most effective pathway, boosted throughout enhanced cellular contacts with infected CD4(+) T cells. Our results suggest that in lymphoid tissues, mDC viral uptake could occur either by encountering cell-free or cell-associated virus produced by infected cells generating the perfect scenario to promote HIV pathogenesis and impact disease progression.

Keywords: Dendritic cells, HIV-1, Live cell imaging, Trans-infection