Brain and cervical lymph nodes dendritic cells during central nervous system infection.

Dendritic cells (DCs) are a subset of leukocytes which promote the immune response by antigenpresentation to T cells. In the central nervous system (CNS), DCs are poorly explored during inflammation and infection. Both DCs and brain–derived antigens are drained by cerebrospinal fluid in the afferent lymphatic vessels of cervical lymph nodes, where antigen presentation mainly occurs. We recently demonstrated that in the thy1GFP-M transgenic mice DCs express green fluorescent protein ( GFP ) . These mice represent, therefore, a novel animal model for the study of DCs in vivo by two-photon microscopy ( TPM) . Here, we investigated DCs in an experimental model of CNS infection represented by African trypanosomiasis, also known as sleeping sickness. The causative agent of this disease, which is deadly if untreated, is the parasite Trypanosoma brucei ( Tb ) . After infection, the disease evolves from a first, hemolymphatic stage, to a second, menigoencephalitic stage, in which both T cells and parasites cross the blood-brain barrier and enter the brain parenchyma by mechanisms that still require full clarification. Our aim was understand whether DCs lead upstream events for T cells/Tb neuroinvasion. In vivo transcranial acquisition by TPM in thy1GFP-M mice infected with fluorescent trypanosomes ( DsRed Tb ) showed, during the hemolymphatic stage, direct interactions in the blood vessels between DCs and Ds-Red Tb, possibly representing antigen capture events. Moreover, during the early meningoencephalitic stage, we found that DCs are recruited from the blood and invade the brain parenchyma, where they exhibit random motions. At an advanced phase of the disease, DCs are mainly arranged in static clusters which incorporate the parasite. Confocal analysis showed that the sub-capsular zone of cervical lymph nodes, where DCs are rare or absent in basal conditions, is invaded by migratory DCs during the late meningoencephalitic stage; at the same time point, both migratory and resident DCs preferentially contact CD8+ T cells, probably to present Tb antigens and to prime the immune-response. The present findings provide for the first time evidence of a dynamic role of DCs during CNS infection and point to a role of DCs in mechanisms of pathogen neuroinvasion.