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Topic 11 Macrophage

  • Origin:
    • ==Microglia==: most tissue-resident macrophages, including microglia, originate from the Tolk Sac during embryonic development. not bone marrow
    • ==Monocyte==: Derived from bone marrow --> develop to macrophage when needed
  • Macrophage depend on CSF1R (Colony Stimulating factor 1 receptor) for survival
    • Ligands 1: CSF-1, the general ligand
    • Ligand 2: IL-34, for brain and Skin local macrophages

In brain

  • Microglia contribute to ==Synaptic pruning==: eat the weak connections between neural cells to refine the circuits; in a healthy brain, this is during infant
  • Mechanism: complement Cascade
    • Step 1 (Tagging): The neuron marks a weak synapse with C1q ("Eat me").
    • Step 2 (Opsonization): C1q triggers C3, which coats the synapse.
    • Step 3 (Engulfment): Microglia express the receptor CR3 (also called CD11b/CD18). CR3 locks onto C3 and engulfs the synapse.

Autism -ASD

  • Under-Pruning Hypothesis: lack of pruning will cause Autism
  • If a mother gets a severe infection or inflammation during pregnancy, and let high level of IL-6 cross the placenta: incorrectly prune

Alzheimer's Disease

  • The protective phase
    • Microglia can clear Amyloid-beta plaques
    • ApoE can help microglia to recognize it.
  • The destructive phase
    • Synaptic Pruning ==Reactivation==: the previous microglia synaptic pruning activated again
    • Microglia start eating healthy synapses causing memory loss.