Roddie, H.G., Armitage, E.L., Coates, J.A. et al. (2 more authors) (2019) Simu-dependent clearance of dying cells regulates macrophage function and inflammation resolution. PLoS Biology, 17 (5). e2006741. ISSN 1544-9173
Abstract
Macrophages encounter and clear apoptotic cells during normal development and homeostasis, including at numerous sites of pathology. Clearance of apoptotic cells has been intensively studied, but the effects of macrophage–apoptotic cell interactions on macrophage behaviour are poorly understood. Using Drosophila embryos, we have exploited the ease of manipulating cell death and apoptotic cell clearance in this model to identify that the loss of the apoptotic cell clearance receptor Six-microns-under (Simu) leads to perturbation of macrophage migration and inflammatory responses via pathological levels of apoptotic cells. Removal of apoptosis ameliorates these phenotypes, while acute induction of apoptosis phenocopies these defects and reveals that phagocytosis of apoptotic cells is not necessary for their anti-inflammatory action. Furthermore, Simu is necessary for clearance of necrotic debris and retention of macrophages at wounds. Thus, Simu is a general detector of damaged self and represents a novel molecular player regulating macrophages during resolution of inflammation.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2019 Roddie et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. https://creativecommons.org/licenses/by/4.0/ |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Sheffield Teaching Hospitals |
Funding Information: | Funder Grant number MEDICAL RESEARCH COUNCIL C0494 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 16 May 2019 16:03 |
Last Modified: | 16 May 2019 16:03 |
Status: | Published |
Publisher: | Public Library of Science (PLoS) |
Refereed: | Yes |
Identification Number: | 10.1371/journal.pbio.2006741 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:146214 |