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Tight nanoscale clustering of Fcγ receptors using DNA origami promotes phagocytosis

Macrophages destroy pathogens and diseased cells through Fcγ receptor (FcγR)-driven phagocytosis of antibody-opsonized targets. Phagocytosis requires activation of multiple FcγRs, but the mechanism controlling the threshold for response is unclear. We developed a DNA origami-based engulfment system...

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Detalles Bibliográficos
Autores principales: Kern, Nadja, Dong, Rui, Douglas, Shawn M, Vale, Ronald D, Morrissey, Meghan A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175083/
https://www.ncbi.nlm.nih.gov/pubmed/34080973
http://dx.doi.org/10.7554/eLife.68311
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author Kern, Nadja
Dong, Rui
Douglas, Shawn M
Vale, Ronald D
Morrissey, Meghan A
author_facet Kern, Nadja
Dong, Rui
Douglas, Shawn M
Vale, Ronald D
Morrissey, Meghan A
author_sort Kern, Nadja
collection PubMed
description Macrophages destroy pathogens and diseased cells through Fcγ receptor (FcγR)-driven phagocytosis of antibody-opsonized targets. Phagocytosis requires activation of multiple FcγRs, but the mechanism controlling the threshold for response is unclear. We developed a DNA origami-based engulfment system that allows precise nanoscale control of the number and spacing of ligands. When the number of ligands remains constant, reducing ligand spacing from 17.5 nm to 7 nm potently enhances engulfment, primarily by increasing efficiency of the engulfment-initiation process. Tighter ligand clustering increases receptor phosphorylation, as well as proximal downstream signals. Increasing the number of signaling domains recruited to a single ligand-receptor complex was not sufficient to recapitulate this effect, indicating that clustering of multiple receptors is required. Our results suggest that macrophages use information about local ligand densities to make critical engulfment decisions, which has implications for the mechanism of antibody-mediated phagocytosis and the design of immunotherapies.
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spelling pubmed-81750832021-06-04 Tight nanoscale clustering of Fcγ receptors using DNA origami promotes phagocytosis Kern, Nadja Dong, Rui Douglas, Shawn M Vale, Ronald D Morrissey, Meghan A eLife Cell Biology Macrophages destroy pathogens and diseased cells through Fcγ receptor (FcγR)-driven phagocytosis of antibody-opsonized targets. Phagocytosis requires activation of multiple FcγRs, but the mechanism controlling the threshold for response is unclear. We developed a DNA origami-based engulfment system that allows precise nanoscale control of the number and spacing of ligands. When the number of ligands remains constant, reducing ligand spacing from 17.5 nm to 7 nm potently enhances engulfment, primarily by increasing efficiency of the engulfment-initiation process. Tighter ligand clustering increases receptor phosphorylation, as well as proximal downstream signals. Increasing the number of signaling domains recruited to a single ligand-receptor complex was not sufficient to recapitulate this effect, indicating that clustering of multiple receptors is required. Our results suggest that macrophages use information about local ligand densities to make critical engulfment decisions, which has implications for the mechanism of antibody-mediated phagocytosis and the design of immunotherapies. eLife Sciences Publications, Ltd 2021-06-03 /pmc/articles/PMC8175083/ /pubmed/34080973 http://dx.doi.org/10.7554/eLife.68311 Text en © 2021, Kern et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Kern, Nadja
Dong, Rui
Douglas, Shawn M
Vale, Ronald D
Morrissey, Meghan A
Tight nanoscale clustering of Fcγ receptors using DNA origami promotes phagocytosis
title Tight nanoscale clustering of Fcγ receptors using DNA origami promotes phagocytosis
title_full Tight nanoscale clustering of Fcγ receptors using DNA origami promotes phagocytosis
title_fullStr Tight nanoscale clustering of Fcγ receptors using DNA origami promotes phagocytosis
title_full_unstemmed Tight nanoscale clustering of Fcγ receptors using DNA origami promotes phagocytosis
title_short Tight nanoscale clustering of Fcγ receptors using DNA origami promotes phagocytosis
title_sort tight nanoscale clustering of fcγ receptors using dna origami promotes phagocytosis
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175083/
https://www.ncbi.nlm.nih.gov/pubmed/34080973
http://dx.doi.org/10.7554/eLife.68311
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