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

Area of Science:

• Cell Biology
• Immunology
• Biophysics

Background:

• Podosomes are dynamic actin-rich cellular structures involved in cell migration and extracellular matrix interaction.
• Dendritic cells (DCs) are crucial antigen-presenting cells (APCs) that initiate adaptive immune responses.
• Understanding how DCs sample antigens across physical barriers is vital for immune surveillance.

Purpose of the Study:

• To investigate the role of podosomes in antigen sampling by human dendritic cells.
• To elucidate the mechanisms by which DCs interact with and internalize antigens across epithelial barriers.

Main Methods:

• Utilized gelatin-impregnated porous polycarbonate filters to mimic epithelial barriers.
• Observed DC podosome localization and behavior in response to physical resistance using microscopy.
• Analyzed the molecular composition of podosome-derived structures using endocytic and early endosomal markers.
• Performed functional uptake experiments to assess antigen internalization facilitated by podosomes.

Main Results:

• Mechanosensitive DC podosomes preferentially localized to low-resistance regions, such as filter pores.
• Podosomes protruded into pores and formed structures containing endocytic markers and pathogen recognition receptors (PRRs).
• PRRs within these podosome-derived structures were shown to facilitate antigen uptake from the opposite side of the filter.

Conclusions:

• Podosomes play a novel role in antigen sampling by dendritic cells across epithelial barriers.
• The presence of PRRs in podosome-derived structures suggests a direct role in recognizing and capturing antigens.
• This mechanism provides insight into how immune cells survey environmental antigens in tissues like the lung and gut.