Splenic differentiation and emergence of CCR5+CXCL9+CXCL10+ monocyte-derived dendritic cells in the brain during cerebral malaria

Abstract

Dendritic cells have an important role in immune surveillance. After being exposed to microbial components, they migrate to secondary lymphoid organs and activate T lymphocytes. Here we show that during mouse malaria, splenic inflammatory monocytes differentiate into monocyte-derived dendritic cells (MO-DCs), which are CD11b⁺F4/80⁺CD11c⁺MHCII^highDC-SIGN^highLy6c⁺ and express high levels of CCR5, CXCL9 and CXCL10 (CCR5⁺CXCL9/10⁺ MO-DCs). We propose that malaria-induced splenic MO-DCs take a reverse migratory route. After differentiation in the spleen, CCR5⁺CXCL9/10⁺ MO-DCs traffic to the brain in a CCR2-independent, CCR5-dependent manner, where they amplify the influx of CD8⁺ T lymphocytes, leading to a lethal neuropathological syndrome.