Watching in vivo dendritic cells in action in the brain

Dendritic cells (DCs) present self or no-self antigens to T cells, to modulate the immune response. DCs are widely studied in peripheral organs, but little is known about their function in the brain. We recently demonstrated (Laperchia et al., 2013) that DCs can be monitored in vivo by two-photon microscopy in thy1GFP-M transgenic mice, in which a subset of DCs is tagged by green fluorescent protein (GFP-DCs). Here we investigated by two-photon microscopy the migratory pattern of brain GDP-DCs both in basal condition and during the meningo-encephalitic stage of an experimental model of African trypanosomiasis, also known as sleeping sickness, induced by the infection with parasites Trypanosome brucei brucei. Trough a chronically implanted brain window in thy1GFP-M mice we found, in basal conditions, GFP-DCs floating in the cerebrospinal fluid or static at the pia mater/parenchyma interface. At an early stage of the meningoencephalitis, circulating GFP-DCs were in contact with the parasites, maybe representing an antigen capture process. Subsequently, DCs roll and crawl on the inflamed endothelium and were massively recruited from the blood stream to the brain parenchyma, where exhibited rapid and wide displacements. At a late stage, the number of motile GFP-DCs was significantly reduced and, interestingly, GFP-DCs were mainly arranged in static clusters that incorporate the parasite. Our results show for the first time the migratory pattern of DCs during invasion of the inflamed brain and suggest a role of brain DCs in the passage from brain immune-resistance to immune-tolerance during a parasitic infection