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Commun Integr Biol. 2014 Nov 11;7(5). doi: 10.4161/cib.29084. eCollection 2014 Oct.

Reaching for far-flung antigen: How solid-core podosomes of dendritic cells transform into protrusive structures.

Communicative & integrative biology

Maksim V Baranov, Martin Ter Beest, Geert van den Bogaart

Affiliations

  1. Department of Tumor Immunology; Radboud University Medical Center ; Radboud Institute for Molecular Life Sciences ; Nijmegen, The Netherlands.

PMID: 26843902 PMCID: PMC4594491 DOI: 10.4161/cib.29084

Abstract

We recently identified a novel role for podosomes in antigen sampling. Podosomes are dynamic cellular structures that consist of point-like concentrations of actin surrounded by integrins and adaptor proteins such as vinculin and talin. Podosomes establish cellular contact with the extracellular matrix (ECM) and facilitate cell migration via ECM degradation. In our recent paper, we studied podosomes of human dendritic cells (DCs), major antigen presenting cells (APC) that take-up, process, and present foreign antigen to naive T-cells. We employed gelatin-impregnated porous polycarbonate filters to demonstrate that the mechanosensitive podosomes of DCs selectively localize to regions of low-physical resistance such as the filter pores. After degradation of the gelatin, podosomes increasingly protrude into the lumen of these pores. These protrusive podosome-derived structures contain several endocytic and early endosomal markers such as clathrin, Rab5, and VAMP3, and, surprisingly, also contain C-type lectins, a type of pathogen recognition receptors (PRRs). Finally, we performed functional uptake experiments to demonstrate that these PRRs facilitate uptake of antigen from the opposite side of the filter. Our data provide mechanistic insight in how dendritic cells sample for antigen across epithelial barriers for instance from the lumen of the lung and gut.

Keywords: Actin; Antigen sampling; C-type lectins; Dendritic cell; Invadopodia; Leukocyte extravasation; Membrane trafficking; Pattern recognition receptors; Podosome; Receptor-mediated endocytosis

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