Force-bearing phagocytic adhesion rings mediate the phagocytosis of surface-bound particles

Abstract Many micro-particles including pathogens strongly adhere to hosts. It remains elusive how macrophages detach these surface-bound particles during phagocytosis. We show that, rather than binding directly to these particles, macrophages form unique β2 integrin-mediated adhesion structures at...

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Main Authors: Subhankar Kundu, Kaushik Pal, Arghajit Pyne, Xuefeng Wang
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-56404-w
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author Subhankar Kundu
Kaushik Pal
Arghajit Pyne
Xuefeng Wang
author_facet Subhankar Kundu
Kaushik Pal
Arghajit Pyne
Xuefeng Wang
author_sort Subhankar Kundu
collection DOAJ
description Abstract Many micro-particles including pathogens strongly adhere to hosts. It remains elusive how macrophages detach these surface-bound particles during phagocytosis. We show that, rather than binding directly to these particles, macrophages form unique β2 integrin-mediated adhesion structures at the cell-substrate interfaces, specifically encircling the surface-bound particles. These circular adhesion structures that we named phagocytic adhesion rings (PARs) serve as strongholds to support local ring-shaped actin structures constricting into the particle-substrate cleavages, thereby pinching off the particles from the substrate. During this process, integrins in PARs sustain tensions due to the reaction force of actin polymerization against the particles. Such tensions are critical for phagocytic efficiency of surface-bound particles. PARs were formed in all tested macrophages (mouse, human and fish) and micron-sized particles (microbeads and E. coli), demonstrating their conserved role in the phagocytosis. This study reveals a mechanism of PAR-mediated phagocytosis, specialized for the detachment and internalization of surface-bound particles.
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spelling doaj-art-f6156b461ab14da6bb8b096efec651582025-01-26T12:41:53ZengNature PortfolioNature Communications2041-17232025-01-0116111810.1038/s41467-025-56404-wForce-bearing phagocytic adhesion rings mediate the phagocytosis of surface-bound particlesSubhankar Kundu0Kaushik Pal1Arghajit Pyne2Xuefeng Wang3Hoxworth Center, College of Medicine, University of CincinnatiDepartment of Chemistry, Indian Institute of Technology TirupatiHoxworth Center, College of Medicine, University of CincinnatiHoxworth Center, College of Medicine, University of CincinnatiAbstract Many micro-particles including pathogens strongly adhere to hosts. It remains elusive how macrophages detach these surface-bound particles during phagocytosis. We show that, rather than binding directly to these particles, macrophages form unique β2 integrin-mediated adhesion structures at the cell-substrate interfaces, specifically encircling the surface-bound particles. These circular adhesion structures that we named phagocytic adhesion rings (PARs) serve as strongholds to support local ring-shaped actin structures constricting into the particle-substrate cleavages, thereby pinching off the particles from the substrate. During this process, integrins in PARs sustain tensions due to the reaction force of actin polymerization against the particles. Such tensions are critical for phagocytic efficiency of surface-bound particles. PARs were formed in all tested macrophages (mouse, human and fish) and micron-sized particles (microbeads and E. coli), demonstrating their conserved role in the phagocytosis. This study reveals a mechanism of PAR-mediated phagocytosis, specialized for the detachment and internalization of surface-bound particles.https://doi.org/10.1038/s41467-025-56404-w
spellingShingle Subhankar Kundu
Kaushik Pal
Arghajit Pyne
Xuefeng Wang
Force-bearing phagocytic adhesion rings mediate the phagocytosis of surface-bound particles
Nature Communications
title Force-bearing phagocytic adhesion rings mediate the phagocytosis of surface-bound particles
title_full Force-bearing phagocytic adhesion rings mediate the phagocytosis of surface-bound particles
title_fullStr Force-bearing phagocytic adhesion rings mediate the phagocytosis of surface-bound particles
title_full_unstemmed Force-bearing phagocytic adhesion rings mediate the phagocytosis of surface-bound particles
title_short Force-bearing phagocytic adhesion rings mediate the phagocytosis of surface-bound particles
title_sort force bearing phagocytic adhesion rings mediate the phagocytosis of surface bound particles
url https://doi.org/10.1038/s41467-025-56404-w
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AT arghajitpyne forcebearingphagocyticadhesionringsmediatethephagocytosisofsurfaceboundparticles
AT xuefengwang forcebearingphagocyticadhesionringsmediatethephagocytosisofsurfaceboundparticles