Sprecher
Beschreibung
The central nervous system (CNS) of Drosophila can be considered as an immune-privileged organ that is separated from the remaining body by the blood-brain barrier (BBB). This barrier is formed by occluding junctions established between subperineurial glial cells. The BBB prevents the invasion of pathogens and allows ion and metabolite homeostasis. Upon neuronal injury or infection, CNS glial cells are able to respond by phagocytosis. The involvement of external macrophages in CNS injuries and infection was assumed to be impossible due to the formation of the BBB and the inability of macrophages to migrate across this barrier. Here, we present a novel injury model, where glial but not neuronal immunity induction triggers the infiltration of external macrophages into the CNS of Drosophila.
First, we tested whether bacterial infection triggers an immune response in the nervous system similar to what is seen in other parts of the animal. Indeed, mRNA analysis showed an activation of the Toll as well as immune deficiency (IMD) pathway together with an upregulation of the PDGF/ VEGF-related factor Pvf2. We further demonstrated that induction of the IMD but not of the Toll pathway results in the infiltration of the CNS by macrophages which is mediated through the induction of Pvf2. Transplantation and specific labelling techniques verified that hemolymph-born macrophages invade the CNS. Within the nervous system macrophages are predominantly found in the synaptic neuropil where they phagocytose synapses. We currently study the mechanisms underlying macrophage migration over the BBB and address the balance between detrimental or supportive role of macrophages during CNS immune challenges.