Fig. 5

The action of neuronal TLRs during brain development. a During the first two postnatal weeks in the rodent brain, axon and dendrite outgrowth, as well as synapse formation, take place to establish connections and to build a functional brain. b Programmed cell death also occurs at the same time. DAMPs—including dsRNAs, ssRNAs, and apoptotic bodies—released from the dead neuron can activate TLRs in adjacent neurons. When those adjacent neurons receive the damage signals, they temporarily withdraw their dendrites to avoid growing into an unhealthy environment. The innervated axons from distal neurons likely also sense those damage factors and retract to prevent forming connections to a dead neuron. Meanwhile, activation of TLRs in neurons triggers local release of low levels of inflammatory cytokines and chemokines to attract nearby microglia. After entering the damaged zone, activated microglia engulf the remaining dead neuronal areas. c Once microglia have cleaned up the damaged area, adjacent neurons may regrow their dendrites. Axons projected from distal neurons may also resume extension to find their targets. d Later, the whole system is stabilized and the proper circuitry is established