Clearance by Microglia Depends on Packaging of Phagosomes into a Unique Cellular Compartment

Research output: Contribution to journalArticle

Abstract

Phagocytic immune cells such as microglia can engulf and process pathogens and dying cells with high efficiency while still maintaining their dynamic behavior and morphology. Effective intracellular processing of ingested cells is likely to be crucial for microglial function, but the underlying cellular mechanisms are poorly understood. Using both living fish embryos and mammalian macrophages, we show that processing depends on the shrinkage and packaging of phagosomes into a unique cellular compartment, the gastrosome, with distinct molecular and ultra-structural characteristics. Loss of the transporter Slc37a2 blocks phagosomal shrinkage, resulting in the expansion of the gastrosome and the dramatic bloating of the cell. This, in turn, affects the ability of microglia to phagocytose and migrate toward brain injuries. Thus, this work identifies a conserved crucial step in the phagocytic pathway of immune cells and provides a potential entry point for manipulating their behavior in development and disease.

Details

Authors
  • Ambra Villani
  • Jørgen Benjaminsen
  • Christian Moritz
  • Katrin Henke
  • Jonas Hartmann
  • Nils Norlin
  • Kerstin Richter
  • Nicole L Schieber
  • Tilman Franke
  • Yannick Schwab
  • Francesca Peri
External organisations
  • European Molecular Biology Laboratory Heidelberg
  • Boston Children's Hospital
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell and Molecular Biology

Keywords

  • Animals, Antiporters/genetics, Apoptosis/genetics, Cell Compartmentation/genetics, HeLa Cells, Humans, Macrophages/metabolism, Membrane Transport Proteins/genetics, Mice, Microglia/metabolism, Neurons/metabolism, Phagocytes/ultrastructure, Phagocytosis/genetics, Phagosomes/genetics, RAW 264.7 Cells, Zebrafish/genetics
Original languageEnglish
Pages (from-to)77-88.e7
JournalDevelopmental Cell
Volume49
Issue number1
Publication statusPublished - 2019 Apr 8
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes