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PLoS Biol. 2019 May 14;17(5):e2006741. doi: 10.1371/journal.pbio.2006741. eCollection 2019 May.

Simu-dependent clearance of dying cells regulates macrophage function and inflammation resolution.

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Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom.
The Bateson Centre, University of Sheffield, Sheffield, United Kingdom.
Department of Biomedical Science, University of Sheffield, Sheffield, United Kingdom.


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.

Conflict of interest statement

The authors have declared that no competing interests exist.

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