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

Hannah Grace Roddie1,2, Emma Louise Armitage1,2, Jonathon Alexis Coates1,2,3

  • 1Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom.

Plos Biology
|May 16, 2019
PubMed

Insights

Loss of the Six-microns-under (Simu) receptor impairs macrophage function and inflammatory responses. Simu acts as a general detector of damaged self, crucial for resolving inflammation.

Area of Science:

  • Immunology
  • Developmental Biology
  • Cell Biology

Background:

  • Macrophages clear apoptotic cells during development and disease.
  • The impact of apoptotic cell clearance on macrophage behavior is not well understood.

Purpose of the Study:

  • To investigate the role of the apoptotic cell clearance receptor Six-microns-under (Simu) in macrophage behavior.
  • To understand how macrophage-apoptotic cell interactions influence inflammatory responses.

Main Methods:

  • Utilized Drosophila embryos to study cell death and apoptotic cell clearance.
  • Manipulated cell death and observed effects on macrophage migration and inflammation.
  • Assessed the necessity of phagocytosis for the anti-inflammatory action of apoptotic cells.

Main Results:

  • Loss of Simu perturbs macrophage migration and inflammatory responses when apoptotic cells accumulate.
  • Removing apoptotic cells ameliorates Simu-loss associated defects.
  • Acute induction of apoptosis mimics these defects, even without phagocytosis.
  • Simu is essential for clearing necrotic debris and macrophage wound retention.

Conclusions:

  • Simu is a critical receptor for detecting damaged self and regulating macrophage behavior.
  • Simu plays a novel role in the resolution of inflammation by macrophages.

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