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Long-term In Vivo Tracking of Inflammatory Cell Dynamics Within Drosophila Pupae
Published on: June 14, 2018
Ferroptosis-like cell death promotes and prolongs inflammation in Drosophila
Andrew J Davidson1,2, Rosalind Heron2, Jyotirekha Das3
1Wolfson Wohl Centre for Cancer Research, School of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
Abstract:
Ferroptosis is a distinct form of necrotic cell death caused by overwhelming lipid peroxidation, and emerging evidence indicates a major contribution to organ damage in multiple pathologies. However, ferroptosis has not yet been visualized in vivo due to a lack of specific probes, which has severely limited the study of how the immune system interacts with ferroptotic cells and how this process contributes to inflammation. Consequently, whether ferroptosis has a physiological role has remained a key outstanding question. Here we identify a distinct, ferroptotic-like, necrotic cell death occurring in vivo during wounding of the Drosophila embryo using live imaging. We further demonstrate that macrophages rapidly engage these necrotic cells within the embryo but struggle to engulf them, leading to prolonged, frustrated phagocytosis and frequent corpse disintegration. Conversely, suppression of the ferroptotic programme during wounding delays macrophage recruitment to the injury site, pointing to conflicting roles for ferroptosis during inflammation in vivo.
Insights
Ferroptosis, a cell death form, was visualized in vivo for the first time in Drosophila embryos during wounding. This finding reveals ferroptosis
Area of Science:
- Cell Biology
- Immunology
- Developmental Biology
Background:
- Ferroptosis is a necrotic cell death pathway driven by lipid peroxidation, implicated in organ damage.
- In vivo visualization of ferroptosis has been lacking, hindering studies on its immune interactions and physiological roles.
- Understanding ferroptosis in vivo is crucial for deciphering its contribution to inflammation and pathology.
Purpose of the Study:
- To visualize ferroptosis-like cell death in vivo.
- To investigate the interaction between immune cells and ferroptotic cells during tissue injury.
- To elucidate the physiological role of ferroptosis in vivo.
Main Methods:
- Live imaging of Drosophila embryo wounding.
- Observation of macrophage-necrotic cell interactions.
- Genetic manipulation to suppress ferroptosis pathways.
Main Results:
- A distinct ferroptosis-like necrotic cell death was identified in vivo during Drosophila embryo wounding.
- Macrophages were observed to interact with these necrotic cells, exhibiting frustrated phagocytosis and corpse disintegration.
- Suppression of ferroptosis delayed macrophage recruitment to the wound site.
Conclusions:
- Ferroptosis can be visualized in vivo, offering new avenues for research.
- Ferroptosis influences immune cell dynamics at injury sites, with complex roles in inflammation.
- The study highlights a physiological role for ferroptosis in development and injury response.

