Tight nanoscale clustering of Fcγ receptors using DNA origami promotes phagocytosis
© 2021, Kern et al..
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.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2021 |
---|---|
Erschienen: |
2021 |
Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
---|---|
Enthalten in: |
eLife - 10(2021) vom: 03. Juni |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Kern, Nadja [VerfasserIn] |
---|
Links: |
---|
Anmerkungen: |
Date Completed 19.10.2021 Date Revised 03.12.2021 published: Electronic Citation Status MEDLINE |
---|
doi: |
10.7554/eLife.68311 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM326293469 |
---|
LEADER | 01000naa a22002652 4500 | ||
---|---|---|---|
001 | NLM326293469 | ||
003 | DE-627 | ||
005 | 20231225194300.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231225s2021 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.7554/eLife.68311 |2 doi | |
028 | 5 | 2 | |a pubmed24n1087.xml |
035 | |a (DE-627)NLM326293469 | ||
035 | |a (NLM)34080973 | ||
035 | |a (PII)e68311 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Kern, Nadja |e verfasserin |4 aut | |
245 | 1 | 0 | |a Tight nanoscale clustering of Fcγ receptors using DNA origami promotes phagocytosis |
264 | 1 | |c 2021 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 19.10.2021 | ||
500 | |a Date Revised 03.12.2021 | ||
500 | |a published: Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a © 2021, Kern et al. | ||
520 | |a 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 | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, N.I.H., Extramural | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 4 | |a Video-Audio Media | |
650 | 4 | |a Antibody | |
650 | 4 | |a DNA origami | |
650 | 4 | |a Fc Receptor | |
650 | 4 | |a Phagocytosis | |
650 | 4 | |a cell biology | |
650 | 4 | |a human | |
650 | 4 | |a immunology | |
650 | 4 | |a immunotherapy | |
650 | 4 | |a inflammation | |
650 | 4 | |a mouse | |
650 | 4 | |a synthetic biology | |
650 | 7 | |a Ligands |2 NLM | |
650 | 7 | |a Receptors, Chimeric Antigen |2 NLM | |
650 | 7 | |a Receptors, IgG |2 NLM | |
650 | 7 | |a DNA |2 NLM | |
650 | 7 | |a 9007-49-2 |2 NLM | |
700 | 1 | |a Dong, Rui |e verfasserin |4 aut | |
700 | 1 | |a Douglas, Shawn M |e verfasserin |4 aut | |
700 | 1 | |a Vale, Ronald D |e verfasserin |4 aut | |
700 | 1 | |a Morrissey, Meghan A |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t eLife |d 2012 |g 10(2021) vom: 03. Juni |w (DE-627)NLM221831460 |x 2050-084X |7 nnns |
773 | 1 | 8 | |g volume:10 |g year:2021 |g day:03 |g month:06 |
856 | 4 | 0 | |u http://dx.doi.org/10.7554/eLife.68311 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 10 |j 2021 |b 03 |c 06 |