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

脑型疟疾期间脾脏分化并出现 CCR5+CXCL9+CXCL10+ 单核细胞衍生的树突状细胞

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作者:Isabella C Hirako, Marco A Ataide, Lucas Faustino, Patricia A Assis, Elizabeth W Sorensen, Hisashi Ueta, Natalia M Araújo, Gustavo B Menezes, Andrew D Luster, Ricardo T Gazzinelli

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+MHCIIhighDC-SIGNhighLy6c+ 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.

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