Infiltrating monocytes trigger EAE progression, but do not contribute to the resident microglia pool

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.