Brain inflammation triggers macrophage invasion across the blood-brain barrier in Drosophila during pupal stages

The nervous system is shielded from circulating immune cells by the blood-brain barrier (BBB). During infections and autoimmune diseases, macrophages can enter the brain where they participate in pathogen elimination but can also cause tissue damage. Here, we establish a Drosophila model to study macrophage invasion into the inflamed brain. We show that the immune deficiency (Imd) pathway, but not the Toll pathway, is responsible for attraction and invasion of hemolymph-borne macrophages across the BBB during pupal stages. Macrophage recruitment is mediated by glial, but not neuronal, induction of the Imd pathway through expression of Pvf2. Within the brain, macrophages can phagocytose synaptic material and reduce locomotor abilities and longevity. Similarly, we show that central nervous system infection by group B Streptococcus elicits macrophage recruitment in an Imd-dependent manner. This suggests that evolutionarily conserved inflammatory responses require a delicate balance between beneficial and detrimental activities.

Automated summary

The study reveals that macrophages can enter the brain during infections and autoimmune diseases, participating in pathogen elimination but also potentially causing tissue damage. Through a Drosophila model, it was found that the immune deficiency pathway plays a role in attracting and invading macrophages into the brain.