Microglia and Neuroinflammation
A microglial cell dies within days if you block one receptor. Not impaired — dead. CSF1R signalling is a continuous survival requirement, not a growth factor the cell can do without, and that single fact makes microglia the only CNS cell type you can delete pharmacologically and then watch repopulate. Everything else on this map hangs off it: an identity maintained by the environment, a sensome pointed at neurons, a TREM2–DAP12 arm that Alzheimer's genetics keeps implicating, and a complement system that prunes synapses in development and re-runs the same programme in disease. Click any protein for the matching Assay Genie ELISA kit or In Vivo antibody.
Identity is maintained by the environment, not inherited. Microglia are yolk-sac derived and self-renewing, but the markers that define them — P2RY12, TMEM119, high CX3CR1 — are not fixed traits. They are a transcriptional state held in place by CNS-specific signals, chiefly IL-34 acting on CSF1R and TGF-β. Take a microglial cell out of the brain and it loses that signature within hours; put a monocyte into the brain and it acquires part of it. This is why "is this cell a microglial cell or an infiltrating monocyte?" is a harder question than it sounds, and why a single marker never settles it.
CSF1R is a survival dependency, and that is the intervention. Blocking CSF1R depletes more than 90% of microglia within a week, and withdrawal lets them repopulate from the survivors. No other CNS population can be removed and restored this cleanly, which is why CSF1R inhibition has become the standard way to ask whether microglia are required for a phenotype rather than merely present during it. Note the ligand split: IL-34 is the dominant CSF1R ligand in brain while M-CSF dominates elsewhere, so the two ligands are not interchangeable readouts.
Complement prunes synapses, and disease re-runs the programme. C1q tags weak synapses, C3 is deposited, and microglial CR3 (CD11b paired with CD18) engulfs them. That is normal development. In ageing and in models of Alzheimer's and glaucoma the same cascade reactivates and removes healthy synapses, and synapse loss — not plaque burden — is what correlates with cognitive decline. Separately, MERTK with its ligand GAS6 handles apoptotic-cell clearance, a distinct and largely non-inflammatory route: which receptor did the eating changes whether the cell responds at all.
The TREM2 arm is where the genetics point. TREM2 signals through DAP12 to SYK and PLCγ2, and rare variants in TREM2 and PLCG2 shift Alzheimer's risk in opposite directions — loss-of-function up, a hypermorphic PLCG2 allele down. That pathway licenses the disease-associated microglia state: osteopontin, Dectin-1, CD11c, LPL, high CD68. Whether DAM is protective or harmful is still contested, and the honest position is that it is probably protective early and harmful late. The In Vivo tie-in: 9 of 37 nodes carry a functional-grade antibody, and the important one is CSF1R itself — available in low and ultra-low endotoxin, which matters because LPS activates the very cells you are counting. The rest of the blockable layer is the output (TNF, IL-1β, IL-1R1, IL-10, GM-CSF) plus CD11b, CD68 and the CD200 brake. The sensome and the TREM2 arm are measurable, not blockable, and it is worth saying so. For research use only; not for use in diagnostic or therapeutic procedures.
Every protein node links to a product — ELISA kit, In Vivo antibody or research antibody.