Synapse - β2 integrins impose a mechanical checkpoint on macrophage phagocytosis

β2 integrins impose a mechanical checkpoint on macrophage phagocytosis Journal Article

Authors:	Settle, A. H.; Winer, B. Y.; de Jesus, M. M.; Seeman, L.; Wang, Z.; Chan, E.; Romin, Y.; Li, Z.; Miele, M. M.; Hendrickson, R. C.; Vorselen, D.; Perry, J. S. A.; Huse, M.
Article Title:	β2 integrins impose a mechanical checkpoint on macrophage phagocytosis
Abstract:	Phagocytosis is an intensely physical process that depends on the mechanical properties of both the phagocytic cell and its chosen target. Here, we employed differentially deformable hydrogel microparticles to examine the role of cargo rigidity in the regulation of phagocytosis by macrophages. Whereas stiff cargos elicited canonical phagocytic cup formation and rapid engulfment, soft cargos induced an architecturally distinct response, characterized by filamentous actin protrusions at the center of the contact site, slower cup advancement, and frequent phagocytic stalling. Using phosphoproteomics, we identified β2 integrins as critical mediators of this mechanically regulated phagocytic switch. Macrophages lacking β2 integrins or their downstream effectors, Talin1 and Vinculin, exhibited specific defects in phagocytic cup architecture and selective suppression of stiff cargo uptake. We conclude that integrin signaling serves as a mechanical checkpoint during phagocytosis to pair cargo rigidity to the appropriate mode of engulfment. © The Author(s) 2024.
Keywords:	signal transduction; controlled study; unclassified drug; human cell; nonhuman; animal cell; mouse; animal; metabolism; animals; mice; mice, knockout; actin; animal tissue; signaling; embryo; animal experiment; proteomics; mice, inbred c57bl; c57bl mouse; regulatory mechanism; cell cycle checkpoint; macrophage; phagocytosis; actins; macrophages; ex vivo study; knockout mouse; phagocyte; rigidity; cell; microglia; hydrogel; vinculin; cd18 antigen; phosphoproteomics; talin; cell phagocytosis; human; male; female; article; bone marrow derived macrophage; cd18 antigens; talin1 protein; tln1 protein, mouse; mechanical property
Journal Title:	Nature Communications
Volume:	15
ISSN:	2041-1723
Publisher:	Nature Publishing Group
Date Published:	2024-09-18
Start Page:	8182
Language:	English
DOI:	10.1038/s41467-024-52453-9
PUBMED:	39294148
PROVIDER:	scopus
PMCID:	PMC11411054
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85204304721&doi=10.1038%2fs41467-024-52453-9&partnerID=40&md5=4e0525184c0413f104ab0d455f59c687
Notes:	The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Corresponding authors is MSK author: Morgan Huse -- Source: Scopus