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Updated: Jan 2, 2026
Analysis of Microglia and Monocyte-derived Macrophages from the Central Nervous System by Flow Cytometry
Published on: June 22, 2017
Infiltrating monocytes trigger EAE progression, but do not contribute to the resident microglia pool
Bahareh Ajami1, Jami L Bennett, Charles Krieger
1University of British Columbia, Biomedical Research Centre, Vancouver, British Columbia, Canada.
Abstract:
In multiple sclerosis and the experimental autoimmune encephalitis (EAE) mouse model, two pools of morphologically indistinguishable phagocytic cells, microglia and inflammatory macrophages, accrue from proliferating resident precursors and recruitment of blood-borne progenitors, respectively. Whether these cell types are functionally equivalent is hotly debated, but is challenging to address experimentally. Using a combination of parabiosis and myeloablation to replace circulating progenitors without affecting CNS-resident microglia, we found a strong correlation between monocyte infiltration and progression to the paralytic stage of EAE. Inhibition of chemokine receptor-dependent recruitment of monocytes to the CNS blocked EAE progression, suggesting that these infiltrating cells are essential for pathogenesis. Finally, we found that, although microglia can enter the cell cycle and return to quiescence following remission, recruited monocytes vanish, and therefore do not ultimately contribute to the resident microglial pool. In conclusion, we identified two distinct subsets of myelomonocytic cells with distinct roles in neuroinflammation and disease progression.
Insights
In experimental autoimmune encephalitis (EAE), infiltrating monocytes, not resident microglia, drive disease progression. Blocking monocyte entry halts EAE, revealing distinct roles for these myelomonocytic cells in neuroinflammation.
Area of Science:
- Neuroimmunology
- Cell Biology
Background:
- Microglia and inflammatory macrophages are phagocytic cells in the central nervous system (CNS) during multiple sclerosis and EAE.
- Their distinct origins (resident precursors vs. blood-borne progenitors) and functional equivalence remain debated.
- Differentiating these cell populations is crucial for understanding neuroinflammation.
Purpose of the Study:
- To experimentally distinguish the roles of microglia and inflammatory macrophages in EAE pathogenesis.
- To investigate the contribution of blood-borne monocyte-derived cells to CNS inflammation and disease progression.
Main Methods:
- Utilized parabiosis and myeloablation to selectively replace circulating progenitors while preserving CNS-resident microglia.
- Monitored EAE progression and correlated it with monocyte infiltration dynamics.
- Investigated the role of chemokine receptor-dependent monocyte recruitment.
Main Results:
- A strong correlation was observed between monocyte infiltration and the paralytic stage of EAE.
- Inhibiting monocyte recruitment to the CNS effectively blocked EAE progression.
- Recruited monocytes disappeared post-remission and did not contribute to the resident microglial pool, unlike microglia which re-entered quiescence.
Conclusions:
- Identified two distinct subsets of myelomonocytic cells with specialized functions in neuroinflammation.
- Demonstrated that infiltrating monocytes, not resident microglia, are essential drivers of EAE pathogenesis.
- Established that recruited monocytes are transient and do not replenish the CNS microglial population.
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