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Microglial Corpse Clearance: Lessons From Macrophages
Mar Márquez-Ropero1,2, Eva Benito1,2,3, Ainhoa Plaza-Zabala1,2
1Achucarro Basque Center for Neuroscience, Parque Científico, University of the Basque Country (UPV/EHU), Leioa, Spain.
Abstract:
From development to aging and disease, the brain parenchyma is under the constant threat of debris accumulation, in the form of dead cells and protein aggregates. To prevent garbage buildup, the brain is equipped with efficient phagocytes: the microglia. Microglia are similar, but not identical to other tissue macrophages, and in this review, we will first summarize the differences in the origin, lineage and population maintenance of microglia and macrophages. Then, we will discuss several principles that govern macrophage phagocytosis of apoptotic cells (efferocytosis), including the existence of redundant recognition mechanisms ("find-me" and "eat-me") that lead to a tight coupling between apoptosis and phagocytosis. We will then describe that resulting from engulfment and degradation of apoptotic cargo, phagocytes undergo an epigenetic, transcriptional and metabolic rewiring that leads to trained immunity, and discuss its relevance for microglia and brain function. In summary, we will show that neuroimmunologists can learn many lessons from the well-developed field of macrophage phagocytosis biology.
Insights
Microglia, the brain's immune cells, clear cellular debris through phagocytosis. Lessons from macrophage biology can advance understanding of microglial function and brain health.
Area of Science:
- Neuroimmunology
- Cellular Biology
- Brain Health
Background:
- The brain parenchyma constantly accumulates cellular debris, necessitating efficient clearance mechanisms.
- Microglia act as the brain's primary phagocytes, similar to tissue macrophages but with distinct characteristics.
Purpose of the Study:
- To compare microglia and macrophages regarding origin, lineage, and population maintenance.
- To elucidate principles governing efferocytosis (phagocytosis of apoptotic cells) by macrophages.
- To explore the concept of trained immunity in phagocytes and its implications for microglia.
Main Methods:
- Review of existing literature on microglia and macrophage biology.
- Analysis of recognition mechanisms (find-me and eat-me signals) in efferocytosis.
- Discussion of epigenetic, transcriptional, and metabolic changes in phagocytes post-engulfment.
Main Results:
- Microglia and macrophages differ in origin, lineage, and population dynamics.
- Efferocytosis involves redundant "find-me" and "eat-me" signals, ensuring efficient clearance of apoptotic cells.
- Phagocytosis induces trained immunity in cells, impacting their function and potentially brain health.
Conclusions:
- Understanding macrophage efferocytosis provides valuable insights into microglial function.
- The study highlights the importance of trained immunity in the context of brain health and disease.
- Neuroimmunology can benefit from established knowledge in macrophage phagocytosis research.
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